|PDF[?] (Download)||Turmeric (Curcuma longa)CurcuminCancer Therapy|
|Date: August 31, 2007||HC# 080471-335|
Re:Curcumin Use in Cancer Therapy Examined
Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy Curr Probl Cancer. July/Aug 2007;31(4):243-305.
This is a detailed, comprehensive review of the effects of curcumin, a constituent of turmeric (Curcuma longa). Turmeric is a dietary spice (the defining component of curry) used in modern folk medicine of India, as well as in Traditional Indian Medicine (Ayurveda) and Traditional Chinese Medicine, to prevent and resolve numerous health problems and promote well-being. It is also a pigment, used in foods. Its characteristic yellow-orange is imparted by curcuminoids, including curcumin, a crystalline powder virtually insoluble in water or ether but soluble in ethanol, diemethylsulfoxide, and acetone. Other curcuminoids are demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin.
Over 1700 papers have been published in the last 50 years on curcumin, first isolated by Vogel in 1815. '[It] reduces blood cholesterol; prevents low-density lipoprotein oxidation; inhibits platelet aggregation; suppresses thrombosis and myocardial infarction; suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease; inhibits HIV replication; enhances wound healing; protects from liver injury; prevents cataract formation; protects from pulmonary toxicity and fibrosis; has therapeutic effects in leishmaniasis; and has antiatherosclerotic activity.'
Curcumin's anti-cancer effects are exerted upon numerous biochemical pathways involved in carcinogenesis, cell proliferation, apoptosis (programmed cell death), metastasis, and angiogenesis. It suppresses growth of several tumor cell lines, including T-cell leukemia and colon cancer lines. Overexpression of cell cycle regulatory proteins 'is the hallmark of cancer.' Curcumin suppresses cyclin D1, overexpressed in many cancers, as well as the Wilms' tumor-1 (WT-1) gene, highly expressed in leukemic blast cells; MEK-1; c-jun; P210 bcr/abl; and hepatocyte growth factor (HGF) and its receptor. '[It] suppresses activation of... transcription factors... implicated in carcinogenesis [including] nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and at least two... signal transducer and activator of transcription proteins (STAT3, STAT5), and modulates... early growth response protein 1 (erg-1), peroxisome proliferation-associated receptor gamma (PPAR-γ), β-catenin, and Nrf-2).' Curcumin downregulates Bcl-2, BclXL, inflammatory enzymes [e.g., cyclooxygenase 2 (COX-2)], matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF), protein kinases, and adhesion molecules. '[C]urcumin exerts its effects in colon cancer cell[s]... by induction of carpases, impairment of Wnt signaling events, inhibition of cell-cell adhesion, and blocking transition of the cell cycle from G2 to M.' High levels of inflammatory chemokines and other metastasis-stimulating events are inhibited by curcumin, as are those promoting angiogenesis.
Curcumin increases the level of enzymes responsible for glutathione synthesis and metabolism as well as glutathione content, 'suggesting... an adaptive response to stress... [B]eneficial effects [of] curcumin appear to be due to changes in the pool of transcription factors that compose EpRE and AP-1 complexes, affecting expression of genes for glutamine-cysteine ligase and other phase II enzymes.' Tumor suppressor gene p53 is a critical regulator of many cellular processes, activating transcription of genes that induce apoptosis in cells with damaged DNA and in cancer cells. Mutant p53 is ineffective, and 'Subjects with only one functional copy... are predisposed to cancer and usually develop several independent tumors... Curcumin has been shown to be a potent inhibitor of p53... In a study of melanoma cells, curcumin induced apoptosis independent of... p53 expression.' Inhibition of farnesyl protein transferase (FPTase), an intermediate on the mevalonate pathway needed for the isoprenylation of Ras proteins, is another potential mechanism by which curcumin may suppress tumor cell growth.
Curcumin increases chemosensitivity of cancer cells to anti-cancer drugs and to radiation, while protecting healthy cells from radiation's effects.
Orally-ingested curcumin is readily bioavailable in animal models, but bioavailability in humans is less clear. Large quantities must be taken before metabolites are found, and then only in feces, suggesting intestinal metabolization. Curcumin is well-tolerated, with only mild side effects (nausea, diarrhea). '[E]xhaustive research and numerous investigations... suggest that curcumin has great potential in the prevention and cure of cancer.' The authors call for development of structural analogs of curcumin with better bioavailability (while allowing that low levels in serum and tissue may account for its positive safety profile), and for large, well-controlled clinical trials. This review can only skim the surface of the material embodied in this extensively referenced paper.