Curcumin and Cancer

A review of the recent research by Dr. Kevin Conners

Turmeric is a popular Indian spice that may have wonderful health benefits for cancer patients. Curcumin (diferuloylmethane) is its major component; Curcuma longa L., a member of the ginger family has long been treasured for its unique flavor it adds to various dishes. Its anti-cancer effects have been studied for numerous tumor activity including colon cancer, breast cancer [1], lung metastases, and brain tumor [2], and because it may inhibit mTOR pathways (discussed below), it may inhibit growth of all cancers.

Curcumin and Cancer 1

Curcumin’s anticancer effect is attributed to its ability to induce normal, programed cell death (apoptosis) in cancer cells without cytotoxic effects on healthy cells, which is very attractive to patients and clinicians. If we can understand that cancer, at its heart, is both an apoptotic failure and an increased replication rate, a nutrient that may help stop both is impressive.

Curcumin interferes with NF-κB [3], a powerful inflammatory pathway that has been linked with numerous inflammatory diseases including cancer [4]. NF-κB has been linked to cancer metastasis which is the primary cause of death in most cancer patients. Curcumin’s ability to limit this and inhibit metastasis is promising.

Curcumin was found to inhibit mTOR complex I which is a major growth pathway that seems to be up-regulated in those with cancer [5]. Understand, mTOR is very important at different times in life. It is highly active in infants and childhood, stimulating rapid growth and development necessary for weight gain and cellular replication; it is activated in wound healing, scar formation, and tissue regeneration. It is necessary to support recovery from injury. However, those with a history of cancer or any active growth do not want increased mTOR function.

There exist numerous exogenous sources that can artificially stimulate mTOR function which cancer patients may want to be aware. Diets high in dairy products may up-regulate mTOR as dairy contains hormones and a chemical known as intrinsic growth factor (IGF-1) that helps baby cows quickly expand their mass and grow.

Protein-rich diets and protein powder drinks may also increase mTOR through glutamine, leucine and arginine. Glutamine both stimulates mTOR directly through the ARF1 pathway and indirectly by regulating cellular uptake of leucine to stimulate mTOR through the RAG pathway. Glutamine also converts to glutamate and this conversion process may be up-regulated should a person have certain genetic defects. Both self-produced as well as exogenous (food-borne) glutamates (MSG) stimulate mTOR function.

Other dietary and environmental concerns exist that increase mTOR. High-fructose corn syrup, pesticide and plastics exposure, and even iron and methylated vitamin supplementation may be at cause. Remember, mTOR stimulates growth and replication of cells, great from growing babies but not for those with cancer. Patients with cancer might best be cautious of environmental exposures that stimulate this pathway.

When we better understand the pathways, what they do and what promotes and inhibits them, we better understand how to help ourselves. The good news is, curcumin may modulate growth of tumor cells by inhibiting mTOR as well as regulating a multitude of other cell signaling pathways. Curcumin was found to help down-regulate the cell proliferation pathway (cyclin D1, c-myc) and directly stimulate apoptosis (cell death) by up-regulating the caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21), and death receptor pathway (DR4, DR5), [6-10]. Curcumin is a real hero for all with cancer.

Researchers Epstein and co-workers had a thorough review on in vitro, [7] citing curcumin as, “non-toxic to human subjects at a high oral dose of up to 12 g/day, and it has anti-inflammatory, antioxidant and anti-cancer properties”. Twelve grams per day is a hefty dose and more than most probably will ever need. One might consider consuming 2-6 grams per day spread over the course of the day. One caution might be to watch any reactions to curcumin as some people with poor gut function may have developed antibodies to turmeric. These individuals may be fine consuming the active C3 form of curcumin with no ill effects.

Other studies show that, when curcumin is combined with other nutrients, a synergistic response may result. Adding sulforaphane (from broccoli seed extract), EPA and DHA (from fish oils), Resveratrol, and EGCg from Green Tea Extract may increase curcumin’s effectiveness [11-15].

 

[1] Bachmeier BE, Mirisola V, Romeo F, Generoso L, Esposito A, Dell’eva R, Blengio F, Killian PH, Albini A, Pfeffer U. Reference profile correlation reveals estrogen-like trancriptional activity of Curcumin. Cell Physiol Biochem. 2010;26(3):471–482.  [PubMed]

[2] Senft C, Polacin M, Priester M, Seifert V, Kogel D, Weissenberger J. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas. BMC Cancer. 2010;10:491. [PMC free article]  [PubMed]

[3] Bachmeier BE, Mohrenz IV, Mirisola V, Schleicher E, Romeo F, Hohneke C, Jochum M, Nerlich AG, Pfeffer U. Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008;29(4):779–789.  [PubMed]

[4] Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2004;1030:434–441.  [PubMed]

[5] Beevers CS, Chen L, Liu L, Luo Y, Webster NJ, Huang S. Curcumin disrupts the Mammalian target of rapamycin-raptor complex. Cancer Res. 2009;69(3):1000–1008. [PMC free article]  [PubMed]

[6] Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? Aaps J. 2009;11(3):495–510. [PMC free article]  [PubMed]

[7] Su CC, Chen GW, Lin JG, Wu LT, Chung JG. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res. 2006;26(2A):1281–1288.  [PubMed]

[8] Chen A, Xu J, Johnson AC. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene. 2006;25(2):278–287.  [PubMed]

[9] Johnson SM, Gulhati P, Arrieta I, Wang X, Uchida T, Gao T, Evers BM. Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling. Anticancer Res. 2009;29(8):3185–3190. [PMC free article]  [PubMed]

[10] Epstein J, Docena G, MacDonald TT, Sanderson IR. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr. 2010;103(6):824–832.[PubMed]

[11] Shen G, Xu C, Hu R, Jain MR, Gopalkrishnan A, Nair S, Huang MT, Chan JY, Kong AN. Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Mol Cancer Ther. 2006;5(1):39–51.  [PubMed]

[12] Yu S, Shen G, Khor TO, Kim JH, Kong AN. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7(9):2609–2620.[PMC free article]  [PubMed]

[13] Cheung KL, Khor TO, Kong AN. Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation. Pharm Res. 2009;26(1):224–231.  [PubMed]

[14] Saw CL, Huang Y, Kong AN. Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol. 2010;79(3):421–430.  [PubMed]

[15] Khor TO, Keum YS, Lin W, Kim JH, Hu R, Shen G, Xu C, Gopalakrishnan A, Reddy B, Zheng X, Conney AH, Kong AN. Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res. 2006;66(2):613–621.[PubMed]