Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC). When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3) in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity.

[1]  Sahdeo Prasad,et al.  Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases , 2017, British journal of pharmacology.

[2]  B. Aggarwal,et al.  γ-Tocotrienol suppresses growth and sensitises human colorectal tumours to capecitabine in a nude mouse xenograft model by down-regulating multiple molecules , 2016, British Journal of Cancer.

[3]  M. Sadelain,et al.  The journey from discoveries in fundamental immunology to cancer immunotherapy. , 2015, Cancer cell.

[4]  B. Aggarwal,et al.  Curcumin, a component of golden spice: from bedside to bench and back. , 2014, Biotechnology advances.

[5]  B. Aggarwal,et al.  Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. , 2013, Molecular nutrition & food research.

[6]  B. Aggarwal,et al.  Multitargeting by turmeric, the golden spice: From kitchen to clinic. , 2013, Molecular nutrition & food research.

[7]  Young Hun Kim,et al.  Aromatic‐turmerone attenuates invasion and expression of MMP‐9 and COX‐2 through inhibition of NF‐κB activation in TPA‐induced breast cancer cells , 2012, Journal of cellular biochemistry.

[8]  Young Hun Kim,et al.  Aromatic-turmerone’s anti-inflammatory effects in microglial cells are mediated by protein kinase A and heme oxygenase-1 signaling , 2012, Neurochemistry International.

[9]  P. Nelson,et al.  Molecular Pathways: Involving Microenvironment Damage Responses in Cancer Therapy Resistance , 2012, Clinical Cancer Research.

[10]  B. Aggarwal,et al.  Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. , 2012, Molecular nutrition & food research.

[11]  L. Zou,et al.  Down-regulation of survivin and hypoxia-inducible factor-1 α by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft. , 2012, Cancer biotherapy & radiopharmaceuticals.

[12]  Chi-Tang Ho,et al.  Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis. , 2011, Molecular nutrition & food research.

[13]  Yitao Wang,et al.  Anti-tumor potential of ethanol extract of Curcuma phaeocaulis Valeton against breast cancer cells. , 2011, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[14]  B. Aggarwal,et al.  Multitargeting by curcumin as revealed by molecular interaction studies. , 2011, Natural product reports.

[15]  S. Kuo,et al.  Cytotoxic Activity and Cell Cycle Analysis of Hexahydrocurcumin on SW 480 Human Colorectal Cancer Cells , 2011, Natural product communications.

[16]  Yitao Wang,et al.  Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis. , 2011, European Journal of Pharmacology.

[17]  B. Aggarwal,et al.  Chemical Composition and Product Quality Control of Turmeric (Curcuma longa L.) , 2011 .

[18]  B. Aggarwal,et al.  NF-κB addiction and its role in cancer: ‘one size does not fit all’ , 2011, Oncogene.

[19]  Sahdeo Prasad,et al.  Turmeric, the golden spice: From traditional medicine to modern medicine , 2011 .

[20]  L. Yao,et al.  Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells. , 2008, European journal of pharmacology.

[21]  Yaqoub Ashhab,et al.  The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. , 2004, Seminars in cancer biology.

[22]  Takashi Tsuruo,et al.  Survival-signaling pathway as a promising target for cancer chemotherapy , 2003, Cancer Chemotherapy and Pharmacology.

[23]  Jen-kun Lin,et al.  Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. , 2000, Biochemical pharmacology.

[24]  J. Duroux,et al.  Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships. , 1998, Cancer letters.

[25]  A. Ingle,et al.  Chemopreventive efficacy of curcumin-free aqueous turmeric extract in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. , 1998, Cancer letters.

[26]  A. Ingle,et al.  Inhibitory effects of curcumin-free aqueous turmeric extract on benzo[a]pyrene-induced forestomach papillomas in mice. , 1997, Cancer letters.

[27]  G. Maru,et al.  Effects of curcumin on the formation of benzo[a]pyrene derived DNA adducts in vitro. , 1995, Cancer letters.

[28]  J. Virol,et al.  INHIBITOR OF APOPTOSIS , 2017 .

[29]  B. Aggarwal,et al.  The Role of Curcumin in Modern Medicine , 2009 .

[30]  S. Nakornchai,et al.  Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. , 2007, Biological & pharmaceutical bulletin.