Users Online: 416

Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Login 
     

   Table of Contents      
REVIEW ARTICLE
Year : 2012  |  Volume : 2  |  Issue : 2  |  Page : 92-99

Pharmacological effects of curcumin


1 Department of Pharmacy, Oman Medical College, Muscat, Oman
2 Research Scholar, Sastra University, Thanjavur, Tamilnadu, India

Date of Submission05-Sep-2011
Date of Acceptance17-Sep-2011
Date of Web Publication9-May-2012

Correspondence Address:
A R Mullaicharam
Pharmacy Department, Oman Medical College, Muscat
Oman
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.95930

Rights and Permissions
   Abstract 

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Cm) is a natural product, which possesses antioxidant, anti-inflammatory, and anti-tumor activities. Curcumin (diferuloylmethane), a low molecular weight polyphenol, derived from the rhizomes of Curcuma spp., has been shown to prevent cancer in the skin, forestomach, duodenum, and colon of mice and in the tongue, colon, mammary glands, and sebaceous glands of rats. Curcumin is a member of curcuminoids isolated from Curcuma longa (turmeric). Currently, it is one of the investigational new drug substances that have great clinical potential. It was used against several ailments in India. Ever since its isolation (mid Nineteenth century), several groups from all over the world worked on its pharmacology.

Keywords: Anti-cancer activity, anti-inflammatory activity, anti-oxidant, curcumin


How to cite this article:
Mullaicharam A R, Maheswaran A. Pharmacological effects of curcumin. Int J Nutr Pharmacol Neurol Dis 2012;2:92-9

How to cite this URL:
Mullaicharam A R, Maheswaran A. Pharmacological effects of curcumin. Int J Nutr Pharmacol Neurol Dis [serial online] 2012 [cited 2019 Oct 19];2:92-9. Available from: http://www.ijnpnd.com/text.asp?2012/2/2/92/95930


   Introduction Top


Curcumin is a multi-functional and pharmacologically safe natural agent. Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family (Zingiberaceae). The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are polyphones and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in a solution. [1]



Chemistry

Curcumin incorporates several functional groups. The aromatic ring systems, which are polyphenols, are connected by two α, β-unsaturated carbonyl groups. The two carbonyl groups form a diketone. The diketones form stable enols or are easily deprotonated and form enolates, while the α,β-unsaturated carbonyl is a good Michael acceptor and undergoes nucleophilic addition. The structure was first identified in 1910, by Kazimierz Kostanecki, J. Miłobędzka, and Wiktor Lampe.

The biosynthetic route of curcumin has proven to be very difficult for researchers to determine. In 1973, Roughly and Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involved a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylized into a curcuminoid. The second mechanism involved two cinnamate units being coupled together by malonyl-CoA. Both mechanisms used cinnamic acid as their starting point, which was derived from the amino acid phenylalanine. This is noteworthy because plant biosyntheses employing cinnamic acid as a starting point are rare compared to the more common use of p-coumaric acid [Figure 1],[Figure 2],[Figure 3],[Figure 4] and [Figure 5]. [3]
Figure 1: Sources of curcumin[2]

Click here to view
Figure 2: Relatives of curcumin[2]

Click here to view
Figure 3: Traditional uses of curcumin

Click here to view
Figure 4: Potential uses of curcumin based on modern technology[2]

Click here to view
Figure 5: How does Curcumin work? modulation of cell signaling by curcumin.[8] From pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets

Click here to view


Anti-cancer activity of curcumin

Curcumin (diferuloylmethane) is a phytochemical that has potent antiproliferative effects against a variety of tumors in vitro. It exerts its effects via diverse biological properties, including, but not limited to, suppression of nuclear factor-nB (NF-nB) and inhibition of angiogenesis. It also enhances the antitumor effects of several classic chemotherapeutic drugs, such as doxorubicin, cis-platinum, and paclitaxel [Figure 6],[Figure 7],[Figure 8] and [Figure 9]. [4],[5],[6]
Figure 6: Curcumin targets.[61] Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins

Click here to view
Figure 7: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins

Click here to view
Figure 8: Proteins, enzymes, receptors modulated by curcumin[61]

Click here to view
Figure 9: Proteins,enzymes, receptors and metals bind with curcumin[8]

Click here to view


Curcumin, derived from the rhizome of Curcuma longa L, having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or post initiation stages. This study has been designed to investigate the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male F344 rats. We also studied the modulating effect of this agent on apoptosis in the tumors. At five weeks of age, groups of male F344 rats were fed a control diet containing no curcumin and an experimental AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%). At seven and eight weeks of age, rats intended for carcinogen treatment were given subcutaneous injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals destined for the promotion/progression study received the AIN-76A control diet for 14 weeks after the second AOM treatment and was then switched to diets containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have developed by week 14, following the AOM treatment. They continued to receive their respective diets until 52 weeks after carcinogen treatment, after which were then sacrificed. The results confirmed our earlier study, in that, administration of 0.2% curcumin during both the initiation and post-initiation periods significantly inhibited colon tumor genesis. In addition, administration of 0.2 and of 0.6% of the synthetic curcumin in the diet during the promotion/progression stage significantly suppressed the incidence and multiplicity of noninvasive adenocarcinomas and also strongly inhibited the multiplicity of invasive adenocarcinomas of the colon. The inhibition of adenocarcinomas of the colon was, in fact, dose-dependent. Administration of curcumin to the rats during the initiation and post-initiation stages and throughout the promotion/progression stage increased apoptosis in the colon tumors as compared to colon tumors in the groups receiving AOM and the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment, as well as when it is given only during the promotion/progression phase (starting late in the premalignant stage) of colon carcinogenesis. [7]

On a pharmacological basis, the role of curcumin in chronic diseases: An age-old spice with modern targets.

Anticancer potential

Curcumin has been shown to exhibit therapeutic potential against a variety of different cancers including leukemia and lymphoma; gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma. The current status of curcumin's anticancer potential against various cancers is systematically analyzed and presented below under different headings.

Breast cancer

Several reports have described the anticarcinogenic activity of curcumin in a variety of breast cancer cell lines. One of our early studies established that the antiproliferative effect of curcumin in human breast cancer cell lines, including hormone-dependent, hormone-independent, and multidrug-resistant cells, was time- and dose-dependent, and correlated with curcumin's inhibition of the ornithine decarboxylase activity. [9] Several mechanisms have been proposed to account for the action of curcumin in breast cancer cells. For example, curcumin was found to inhibit the aryl hydrocarbon receptor and cytochrome P450 1A1; [9] the tyrosine kinase activity of p185neu; the expression of Ki-67, PCNA, p53 mRNAs; and COX-1 and COX-2 enzymes. Curcumin also induced p53-dependent Bax expression, inhibited the vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), [10],[11] disrupted the mitotic spindle structure and induced micro-nucleation. [12] It has been shown to inhibit telomerase activity through human telomerase reverse transcriptase, [13] downregulate the expression of matrix metalloproteinase-2 (MMP-2), upregulate the tissue inhibitor of metalloproteinase-1 (TIMP-1), [14] and block NF-kB and AP-1 activation. [15],[16],[17],[18] Studies have also shown that curcumin inhibits LOX pathways, [19] induces the degradation of cyclin E expression through a ubiquitin-dependent pathway, upregulates cyclin-dependent kinase inhibitors p21 and p27, [20] and downregulates the insulin-like growth factor-1 (IGF-1) [21] in breast cancer cell lines.

Esophageal cancer

Curcumin could be a potential candidate for use in the treatment of esophageal cancer, few studies have examined it in this disease and no in vitro evaluations of its anticancer effects in esophageal cancer cells have been reported. However, curcumin was found to inhibit the cytokine-induced activation of iNOS, JNK, VCAM, and NF-kB in human esophageal microvascular endothelial cells isolated from normal human esophageal tissues, [22] as an inflammatory molecule like NF-kB is over expressed in several tumor tissues; these results may be indirect evidence that curcumin may be effective against esophageal cancer. Two in vivo studies have been reported with curcumin in esophageal cancer. In one, dietary curcumin (500 ppm) fed during the initiation and post-initiation stages inhibited the incidence of esophageal carcinogenesis by 27 and 33%, respectively, in rats. [23] In another study, the efficacy of curcumin as a chemopreventive agent was assessed by measuring the modulation in the incidence of neoplastic change in a rat esophagus. [24]

Intestinal cancer [25]

Thus far, the efficacy of curcumin in intestinal cancer has been shown in a few animal studies. In vivo studies using mouse models have proved that curcumin modifies apoptosis resistance, leading to the inhibition of tumor formation and the prevention of adenoma development in the intestinal tract. The chemopreventive effect of curcumin for intestinal tumors in Min/+ mice was investigated. A dietary level of 0.15% curcumin decreased tumor formation in Min_/_mice by 63%. Examination of intestinal tissue from the treated animals showed that the tumor prevention by curcumin was associated with increased enterocyte apoptosis and proliferation. Curcumin also decreased the expression of the oncoprotein b-catenin in the erythrocytes of the Min/+ mouse, an observation previously associated with an anti-tumor effect.

Hepatic cancer

Curcumin significantly reduced the number of gammaglutamyl transpeptidase-positive foci, a characteristic considered to be the precursor of hepatocellular neoplasm, in rats. Curcumin also had anticarcinogenic effects mediated through the induction of glutathione-linked detoxification enzymes in rat livers. Curcumin also prevented the induction of hepatic hyperplastic nodules, body weight loss, and hypoproteinemia in carcinogen-induced as well as xenograft hepatic cancer models. Both curcumin and curcumin complexed with manganese prevented the increase of hepatic lipid peroxidation, expressed as an MDA level in mice.

Pancreatic cancer

Research over the past decade has indicated that curcumin has an anticarcinogenic effect in various pancreatic cell lines, with numerous mechanisms having been proposed, to account for this effect. In human pancreatic cancer MIA PaCa-2 cells, curcumin was found to inhibit the farnesyl protein transferase. [7] Also, NF-kB was found to be overexpressed in human pancreatic tumor tissues and cell lines; investigators suggested that this overexpression could be inhibited by curcumin because it had the ability to suppress NF-kB expression. [26],[27],[28]

Colorectal cancer

Studies using various colorectal cell lines have proven curcumin's use as a therapeutic agent as it has ability to act through numerous target molecules. For example, curcumin has been shown to disrupt Lovo cells in the S, G2/M phase and interrupt Wnt signaling and adhesion pathways causing G2/M phase arrest and apoptosis in HCT-116 cells, regardless of prostaglandin synthesis. Curcumin-induced apoptosis is a result of PARP cleavage, caspase 3, reduction in Bcl-xL level, and the increased activity of caspase-8, which encourages the Fas signaling of apoptosis. Curcumin reduces the NAT1 mRNA expression and AF-DNA adducts formation in human colon tumor cells. Curcumin has been seen to inhibit the proliferation of cells and induce apoptosis in colorectal cell lines. [9],[29] Risk factors for colon cancer consist of both hereditary and environmental factors. Dietary patterns represent controllable risk factors for the development of colon cancer. Much concentration has focused on declining the threat of colon cancer through the growing intake of dietary fiber; recently, this has incorporated understanding in the use of prebiotics and probiotics. [30]

Bladder cancer

Numerous reports indicate that curcumin has activity against bladder cancer. For example, curcumin has been shown to suppress the proliferation of bladder cancer cells in the culture either through the suppression of NF-kB [31],[32] or through the downregulation of cyclin A and upregulation of p21. [33] Certain synthetic analogs of curcumin have been shown to exhibit activity against bladder cancer cell lines. [34],[35]

Kidney cancer

In human kidney cancer cells, curcumin upregulates apoptotic events such as cell shrinkage, chromatin condensation, and DNA fragmentation [36] and inhibits FPTase. [37] Curcumin serves as a COX-1and COX-2 inhibitor; [38] inhibits microsomal lipid peroxidation and DNA damage; [39] deactivates the Akt pathway; downregulates Bcl-2, Bcl-xL, and IAP proteins; [40] and increases (Tumor Necrosis Factor-Alpha-Related Apoptosis-Inducing Ligand) TRAIL-induced apoptosis by augmenting DR5 expression at the mRNA and protein levels, by producing reactive oxygen species (ROS). [41] In HKC cells, curcumin reduces tumor growth and side effects when activated via the hydrolysis of prodrugs. [34] An in vivo study demonstrated that dietary curcumin treatment reduced risk for kidney cancer metastasis in rats. [42]

Prostate cancer

Curcumin has shown activity against various prostate cancer cells, such as LNCaP, DU145, C4-2B, and PC3. Curcumin can induce programmed cell death in androgen-dependent and androgen-independent prostate cancer cells. It can inhibit capillary tube formation and cell migration and exert significant effects on the actin cytoskeletons in prostate cancer cells. [9],[43],[44],[45]

Cervical cancer

Curcumin modulates the in vitro expression and function of P-gp in multidrug-resistant human KB-V1 cells [9],[46] and sensitizes cisplatin-resistant SiHa cells to cisplatin-induced apoptosis, [47] indicating its ability to reverse MDR in cervical cancer cells. The effect of curcumin in HPV-associated cells was found to involve the downregulation of viral oncogenes, NF-jB and AP-1. [9],[48] Similarly, a major metabolite of curcumin called THC increased the sensitivity of vinblastine, mitoxantrone, and etoposide in a drug-resistant human cervical carcinoma cell line. [49] In a phase I clinical trial, a daily dose, 0.5 - 12 g, of curcumin, taken orally for three months resulted in the histological improvement of precancerous lesions in one out of four patients with uterine cervical intraepithelial neoplasms.

Ovarian cancer

In these ovarian tumors, curcumin alone and with docetaxel decreased both proliferation and micro-vessel density and increased tumor cell apoptosis. In mice with multidrug-resistant ovarian tumors, treatment with curcumin alone and combined with docetaxel resulted in a significant 47 and 58% reductions in tumor growth, respectively. [50]

Pulmonary cancer

Curcumin exhibits anticancer effects in various lung cancer cells through a variety of molecular targets. At the cellular level, curcumin derivatives inhibit FPTase in A549 cells. Curcumin inhibits AP-1 transcription and mediastinal lymph node metastasis in Lewis lung carcinoma cells and ornithine decarboxylase activity in rat tracheal epithelial cells. [51],[52]

Bone cancer

In an in vivo study on rats, dietary curcumin with cisplatin modulated tumor marker indices of fibrosarcoma toward normal controls. Treatment with radiotherapy and curcumin resulted in enhanced tumor cell-killing and reduced radio resistance in mice bearing fibrosarcoma, as indicated by the significant inhibition of radiation-induced ERK and NF-kB expression. [53]

Brain tumor

Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and hemotherapeutic drugs. The therapeutic efficacy of curcumin in various human malignant glioblastoma cells has been established, [54] and curcumin has been found to inhibit the NF-kB signaling pathways in these cell lines. [55],[56],[57] The neuroleptic malignant syndrome is a rare and potentially serious syndrome associated with the use of many antipsychotics, antiparkinsonian drugs, antidepressants, and so on. [58]

Control of cancer symptoms by curcumin

Patients with cancer suffer from various treatment-related symptoms, including neuropathic pain, depression, fatigue, decreased appetite, and sleep disturbance. Many of these symptoms may cause treatment delays and prevent the delivery of full-dose therapy in the scheduled time. In the course of targeting cancer, most chemotherapeutic agents activate NF-kB and induce TNF release. Consequentially, many of the symptoms related to cytokine deregulation are affected by both the disease and the treatment. For example, chemotherapy commonly causes neuropathic pain, depression, fatigue, decreased appetite, and sleep disturbance, all of which have been linked to proinflammatory pathways that include NF-kB and TNF, as well as other key factors, such as IL-1 and IL- 6. [59],[60] Animal models of.'sickness behavior' support this thesis, [61],[62] in that, fluctuations in inflammatory cytokines, primarily IL-1, IL-6, and TNF-a, are related to fluctuations in components of sickness in animals (e.g., anorexia, disturbed sleep, hyperalgesia, and disrupted learning). The administration of these cytokines can produce sickness in behavior, which in turn, can be eliminated by antibodies to these cytokines. The fact of curcumin can suppress the activation of NF-kB and NF-kB-regulated TNF, IL- 1, and IL-6 expression, indicates that it may have a potential effect against these symptoms.

Anti-inflammatory activity of curcumin

Extensive scientific research on curcumin, a natural compound present in the rhizomes of Plant Curcuma Longa Linn., demonstrated its anti-inflammatory action. Curcumin was found to inhibit arachidonic acid metabolism, cyclooxygenase, lipoxygenase, cytokines (Interleukins and tumor necrosis factor), Nuclear factor-κB, and release of steroidal hormones. Curcumin was reported to stabilize the lysosomal membrane and cause uncoupling of oxidative phosphorylation besides having a strong oxygen radical scavenging activity, which was responsible for its anti-inflammatory property. In various animal studies, a dose range of 100 - 200 mg/kg body weight exhibited good anti-inflammatory activity and seemed to have a negligible adverse effect on human systems. Oral LD50 in mice was found to be more than 2.0 g/kg body weight.

Curcumin and anti-inflammatory activity

Arora et al. reported anti-inflammatory activity in different fractions of the petroleum ether extract of Curcuma longa. [64] The total petroleum ether extract of the rhizome of turmeric and two of its fractions A and B were evaluated for their anti-inflammatory activity in albino rats (180 - 200 g) and compared with that of hydrocortisone acetate and phenylbutazone. It was found that the anti-inflammatory activity of the total petroleum ether extract was less than the individual fractions A and B. The fractions were almost as active as hydrocortisone acetate in the inflammation induced by the cotton pellet method. Curcumin isolated from the alcoholic extract of turmeric has been shown to be a useful anti-inflammatory agent. In subacute toxicity experiments, no significant toxic side effects were observed in rats when the extract was administered for four weeks at the dose level of 1 - 2 g/kg. Oral LD50 was found to be 12.2 g/ kg. [64] In recent times, the anti-inflammatory activity of curcumin has been demonstrated in acute and chronic models of inflammation in rats and mice. [65],[66] In rats with Freud's adjuvant-induced arthritis, administration of curcumin significantly reduced the inflammatory swelling compared to the control. [66] Oral doses, up to 160 mg/ kg of curcumin, failed to prevent phenyl quinone-induced inflammation in mice. In instances of acute inflammation, oral administration of curcumin was found to be as effective as cortisone or phenylbutazone, whereas, in chronic inflammation it was only half as effective. [67] Curcumin may also be applied topically to animal skin to counteract inflammation and irritation associated with inflammatory skin conditions and allergies. [67] Curcumin is a more potent antioxidant than Vitamin E. [68]


   Conclusions Top


As detailed in this review, curcumin can modulate multiple cellular signaling pathways and interact with numerous molecular targets. Thus, it may have the potential to act against a large number of cancers. In vitro, in vivo, and human clinical studies have all established curcumin's promise and revealed its therapeutic value. More extensive, randomized clinical trials are now needed. The safety, low cost, and already proven efficacy of this 'age old' natural medicine makes it a promising agent for the treatment of an 'old-age' disease like cancer. [25]

All of the above-mentioned reviews clearly indicate that curcumin can be used for the treatment of inflammatory diseases, different types of infections, and for many chronic diseases.

 
   References Top

1.Tsonko M Kolev, Evelina A.Velcheva, Bistra A.Stamboliyska, Michael Spitetter. DFT and Experimental Studies of the Structure and Vibrational Spectra of Curcumin. Int J Quantum Chem (Wiley Periodicals) 2005;102:1069-79.  Back to cited text no. 1
    
2.Available from: http://www.curcuminresearch.org/whatiscurcumin.html.  Back to cited text no. 2
    
3.Kita T, Imai S, Sawada H, Kumagai H, Seto H. The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors. Biosci Biotechnol Biochem 2008;72:1789-98.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Bava SV, Puliappadamba VT, Deepti A, Nair A, Karunagaran D, Anto RJ. Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-nB and the serine/threonine kinase Akt and is independent of tubulin polymerization. J Biol Chem 2005;280:6301-8.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Chan MM, Fong D, Soprano KJ, Holmes WF, Heverling H. Inhibition of growth and ensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol 2003;194:63-70.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-nB activation levels and in IAP gene expression. Cancer Lett 2005;224:53-65.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive Effect of Curcumin, a Naturally Occurring Anti-Inflammatory Agent, during the Promotion/Progression Stages of Colon Cancer. Cancer Res 1999;59:597-601.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Aggarwal BB, Sung B. Trends, Curcumin: The Indian solid gold. Pharmacol Sci 2009;30:85-94.  Back to cited text no. 8
    
9.Aggarwal BB, Bhatt ID, Ichikawa H, Ahn KS, Sethi G, Sandur SK, et al. Curcumin - biological and medicinal properties. In: Ravindran PN, Babu KN, Sivaraman K, editors. Turmeric the Genus Curcuma. NY: CRC Press; 2007. p. 297-368.  Back to cited text no. 9
    
10.Shao ZM, Shen ZZ, Liu CH, Sartippour MR, Go VL, Heber D, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int J Cancer 2002;98:234-40.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Schindler R, Mentlein R. Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr 2006;136:1477-82.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Holy JM. Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells. Mutat Res 2002;518:71-84.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ. Curcumin inhibits telomerase activity through human telomerase reverse transcriptase in MCF-7 breast cancer cell line. Cancer Lett 2002;184:1-6.  Back to cited text no. 13
[PUBMED]  [FULLTEXT]  
14.Di GH, Li HC, Shen ZZ, Shao ZM. Analysis of antiproliferation of curcumin on human breast cancer cells and its mechanism. Zhonghua Yi Xue Za Zhi 2003;83:1764-8.  Back to cited text no. 14
[PUBMED]    
15.Bobrovnikova-Marjon EV, Marjon PL, Barbash O, Vander Jagt DL, Abcouwer SF. Expression of angiogenic factors vascular endothelial growth factor and interleukin-8/CXCL8 is highly responsive to ambient glutamine availability: Role of nuclear factor-kappaB and activating protein-1. Cancer Res 2004;64:4858-69.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 2005;11:7490-8.  Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.Yoon H, Liu RH. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells. J Agric Food Chem 2007;55:3167-73.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.Bachmeier BE, Mohrenz IV, Mirisola V, Schleicher E, Romeo F, Hohneke C, et al. Curcumin down-regulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappa B. Carcinogenesis 2008;29:779-89.  Back to cited text no. 18
    
19.Hammamieh R, Sumaida D, Zhang X, Das R, Jett M. Control of the growth of human breast cancer cells in culture by manipulation of arachidonate metabolism. BMC Cancer 2007;7:138.  Back to cited text no. 19
[PUBMED]  [FULLTEXT]  
20.Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol 2007;73:1024-32.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Xia X, Cheng G, Pan Y, Xia ZH, Kong LD. Behavioral, neurochemical, neuroendocrine effects of the ethanolic extract from Curcuma longa L.in the mouse forced swimming test. J Ethnopharmacol 2007;110:356-63.  Back to cited text no. 21
[PUBMED]  [FULLTEXT]  
22.Rafiee P, Ogawa H, Heidemann J, Li MS, Aslam M, Lamirand YH, et al. Isolation and characterization of human esophageal microvascular endothelial cells: Mechanisms of inflammatory activation. Am J Physiol Gastrointest Liver Physiol 2003;285: G1277-92.  Back to cited text no. 22
    
23.Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as Curecumin: From kitchen to clinic. Biochem Pharmacol 2008;75:787-809.  Back to cited text no. 23
    
24.Wax JW, Pyhtila RN, Graf R, Nines CW, Boone RR, Dasari MS, et al. Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry. J Biomed Opt 2005;10:051604.  Back to cited text no. 24
    
25.Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Lett 2008;267:133-64.  Back to cited text no. 25
[PUBMED]  [FULLTEXT]  
26.Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 1999;5:119-27.  Back to cited text no. 26
[PUBMED]  [FULLTEXT]  
27.Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R. Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer 2004;101:2351-62.  Back to cited text no. 27
[PUBMED]  [FULLTEXT]  
28.Khanbolooki S, Nawrocki ST, Arumugam T, Andtbacka R, Pino MS, Kurzrock R, et al. Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells. Mol Cancer Ther 2006;5:2251-60.  Back to cited text no. 28
[PUBMED]    
29.Wei SC, Lin YS, Tsao PN, Wu-Tsai JJ, Wu CH, Wong JM. Comparison of the anti-proliferation and apoptosisinduction activities of sulindac, celecoxib, curcumin, and nifedipine in mismatch repair-deficient cell lines. J Formos Med Assoc 2004;103:599-606.  Back to cited text no. 29
[PUBMED]    
30.Saini R. Role of probiotics in colorectal cancer. Int J Nutr Pharmacol Neurol Dis 2011;1:81-2.  Back to cited text no. 30
  Medknow Journal  
31.Sun M, Yang Y, Li H, Su B, Lu Y, Wei Q, et al. [The effect of curcumin on bladder cancer cell line EJ in vitro]. Zhong Yao Cai 2004;27:848-50.  Back to cited text no. 31
[PUBMED]    
32.Kamat AM, Sethi G, Aggarwal BB. Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-kappaB and nuclear factor-kappaB-regulated gene products in IFN-alpha-sensitive and IFN-alpha-resistant human bladder cancer cells. Mol Cancer Ther 2007;6:1022-30.  Back to cited text no. 32
[PUBMED]    
33.Park GY, Kim G.D, Kim BT, Choi YM, Park YH, Choi. Induction of G2/M arrest and inhibition of cyclooxygenase- 2 activity by curcumin in human bladder cancer T24 cells. Oncol Rep 2006;15:1225-31.  Back to cited text no. 33
    
34.Lu P, Tong Q, Jiang F, Zheng L, Chen F, Zeng F, et al. Preparation of curcumin prodrugs and their in vitro anti-tumor activities. J Huazhong Univ Sci Technol Med Sci 2005;25:668-70, 678.  Back to cited text no. 34
[PUBMED]    
35.Tong QS, Zheng LD, Lu P, Jiang FC, Chen FM, Zeng FQ, et al. Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. Anticancer Drugs 2006;17:279-87.  Back to cited text no. 35
[PUBMED]  [FULLTEXT]  
36.Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 1996;26:111-20.  Back to cited text no. 36
[PUBMED]  [FULLTEXT]  
37.Chen X, Hasuma T, Yano Y, Yoshimata T, Morishima Y, Wang Y, et al. Inhibition of farnesyl protein transferase by monoterpene, curcumin derivatives and gallotannin. Anticancer Res 1997;17:2555-64.  Back to cited text no. 37
[PUBMED]    
38.Ramsewak RS, DeWitt DL, Nair MG. Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine 2000;7:303-8.  Back to cited text no. 38
[PUBMED]    
39.Iqbal M, Okazaki Y, Okada S. In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage. Teratog Carcinog Mutagen 2003;Suppl 1:151-60.  Back to cited text no. 39
[PUBMED]  [FULLTEXT]  
40.Woo JH, Kim YH, Choi YJ, Kim DG, Lee KS, Bae JH, et al. Molecular mechanisms of curcumininduced cytotoxicity: Induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl- XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis 2003;24:1199-208.  Back to cited text no. 40
[PUBMED]  [FULLTEXT]  
41.Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK. Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis 2005;26:1905-13.  Back to cited text no. 41
[PUBMED]  [FULLTEXT]  
42.Frank N, Knauft J, Amelung F, Nair J, Wesch H, Bartsch H. No prevention of liver and kidney tumors in Long-Evans Cinnamon rats by dietary curcumin, but inhibition at other sites and of metastases. Mutat Res 2003;523-524:127-35.  Back to cited text no. 42
[PUBMED]  [FULLTEXT]  
43.Shenouda NS, Zhou C, Browning JD, Ansell PJ, Sakla MS, Lubahn DB, et al. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer 2004;49:200-8.  Back to cited text no. 43
[PUBMED]  [FULLTEXT]  
44.Guo H, Yu JH, Chen K, Ye ZQ. [Curcumin-induced the expression of inhibitor kappaB alpha protein in human prostate cancer cells]. Zhonghua Wai Ke Za Zhi 2006;44:1256-9.  Back to cited text no. 44
[PUBMED]    
45.Shankar S, Chen Q, Sarva K, Siddiqui I, Srivastava RK. Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: Molecular mechanisms of apoptosis, migration and angiogenesis. J Mol Signal 2007;2:10.  Back to cited text no. 45
[PUBMED]  [FULLTEXT]  
46.Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV, Limtrakul P. Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from turmeric powder. Biochem Pharmacol 2004;68:2043-52.  Back to cited text no. 46
[PUBMED]  [FULLTEXT]  
47.Venkatraman M, Anto RJ, Nair A, Varghese M, Karunagaran D. Biological and chemical inhibitors of NFkappaB sensitize SiHa cells to cisplatin-induced apoptosis. Mol Carcinog 2005;44:51-9.  Back to cited text no. 47
[PUBMED]  [FULLTEXT]  
48.Divya CS, Pillai MR. Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog 2006;45:320-32.  Back to cited text no. 48
[PUBMED]  [FULLTEXT]  
49.Limtrakul P, Chearwae W, Shukla S, Phisalphong C, Ambudkar SV. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin. Mol Cell Biochem 2007;296:85-95.  Back to cited text no. 49
[PUBMED]  [FULLTEXT]  
50.Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res 2007;13:3423-30.  Back to cited text no. 50
[PUBMED]  [FULLTEXT]  
51.White EL, Ross LJ, Schmid SM, Kelloff GJ, Steele VE, Hill DL. Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea. Oncol Rep 1998;5:717-22.  Back to cited text no. 51
[PUBMED]  [FULLTEXT]  
52.Ichiki K, Mitani N, Doki Y, Hara H, Misaki T, Saiki I. Regulation of activator protein-1 activity in the mediastinal lymph node metastasis of lung cancer. Clin Exp Metastasis 2000;18:539-45.  Back to cited text no. 52
[PUBMED]  [FULLTEXT]  
53.Kumar Mitra A, Krishna M. In vivo modulation of signaling factors involved in cell survival. J Radiat Res (Tokyo) 2004;45:491-5.  Back to cited text no. 53
    
54.Ambegaokar SS, Wu L, Alamshahi K, Lau J, Jazayeri L, Chan S, et al. Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth. Neuro Endocrinol Lett 2003;24:469-73.  Back to cited text no. 54
[PUBMED]    
55.Nagai S, Kurimoto M, Washiyama K, Hirashima Y, Kumanishi T, Endo S. Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. J Neurooncol 2005;74:105-11.  Back to cited text no. 55
[PUBMED]  [FULLTEXT]  
56.Karmakar S, Banik NL, Ray SK. Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem Res 2007;32:2103-13.  Back to cited text no. 56
[PUBMED]  [FULLTEXT]  
57.Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and hemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem 2007;102:522-38.  Back to cited text no. 57
[PUBMED]  [FULLTEXT]  
58.Chakraborty S, Sanyal D, Mukherjee B, Roy S. A case of neuroleptic malignant syndrome induced by desvenlafaxine in a patient on clozapine. Int J Nutr Pharmacol Neurol Dis 2011;1:78-80  Back to cited text no. 58
    
59.Cleeland CS, Bennett GJ, Dantzer R, Dougherty PM, Dunn AJ, Meyers CA, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 2003;97:2919-25.  Back to cited text no. 59
[PUBMED]  [FULLTEXT]  
60.Chen HW, Yu SL, Chen JJ, Li HN, Lin YC, Yao PL, et al. Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol 2004;65:99-110.  Back to cited text no. 60
[PUBMED]  [FULLTEXT]  
61.Dantzer R. Cytokine-induced sickness behavior: Mechanisms and implications. Ann NY Acad Sci 2001;933:222-34.  Back to cited text no. 61
[PUBMED]  [FULLTEXT]  
62.Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 2007;21:153-60.  Back to cited text no. 62
[PUBMED]  [FULLTEXT]  
63.Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 2008;269:199-225.  Back to cited text no. 63
[PUBMED]  [FULLTEXT]  
64.Arora R, Basu N, Kapoor V. Anti-inflammatory studies on Curcuma longa (turmeric). Indian J Med Res 1971;59:1289-95.  Back to cited text no. 64
    
65.Srimal RC, Khanna NM, Dhawan BN. A preliminary report on anti inflammatory activity of curcumin. Int J Pharm 1971;3:10.  Back to cited text no. 65
    
66.Srimal RC, Dhawan BN. Pharamacology of diferuloyl methane, a non steroidal anti-inflammatory drug. J Pharm Pharmacol 1973;25:447.  Back to cited text no. 66
[PUBMED]    
67.Mukhopadhyay A, Basu N, Ghatak N. Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions 1982;12:508-15.  Back to cited text no. 67
    
68.Patro BS, Rele S, Chintalwar GJ, Chattopadhyay S, Adhikari S, Mukherjee T. Protective activities of some phenolic 1,3-diketones against lipid peroxidation: Possible involvement of the 1,3-diketone moiety. Chembiochem 2002;3:364-70.  Back to cited text no. 68
[PUBMED]  [FULLTEXT]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]


This article has been cited by
1 Clinically evaluated cancer drugs inhibiting redox signaling
Lynn Kirkpatrick,Garth Powis
Antioxidants & Redox Signaling. 2016;
[Pubmed] | [DOI]
2 Dietary Botanicals for Chemoprevention of Prostate Cancer
Prasan Bhandari
Journal of Traditional and Complementary Medicine. 2014; 4(2): 75
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Conclusions
    References
    Article Figures

 Article Access Statistics
    Viewed10617    
    Printed301    
    Emailed2    
    PDF Downloaded808    
    Comments [Add]    
    Cited by others 2    

Recommend this journal