Wednesday, March 07, 2007

Curcumin, a Dietary Component, Has Anticancer, Chemosensitization, and Radiosensitization Effects by Down-regulating the MDM2 Oncogene through the PI3





Written by Ricardo Sanchez-Ortiz, MD
Wednesday, 07 March 2007

BERKELEY, CA (UroToday.com) - Curry powder is a mixture predominantly composed of turmeric root extract and other spices such as coriander and fenugreek.

Curcumin, a turmeric root extract, has been shown to possess activity in the treatment and prevention of cancer, multiple sclerosis, and Alzheimer's disease. The molecular mechanism for its anticancer effect is largely unknown, although it is thought to inhibit the synthesis of MDM2, an oncoprotein known to bind p53 and modulate p21 expression.
In the March 1 issue of Cancer Research, Li and colleagues from the Comprehensive Cancer Center of the University of Alabama report on a study designed to elucidate the molecular anticancer effect of curcumin in a preclinical prostate cancer model.

Using PC-3 human prostate cancer cell lines grown in vitro, curcumin was found to decrease the mRNA and protein expression of the oncoprotein MDM2 and to enhance the expression of tumor modulator p21. This translated into an induction of apoptosis and inhibition of proliferation of PC-3 cells grown in culture.

A group of mice xenografts were also developed using the PC-3 cell-line. Curcumin was administered via an oral route to all mice (5 days per week for 4 weeks) except for the control group which only received cottonseed oil. Study groups (5 mice each) were divided as follows: (1) curcumin therapy alone, (2) gemcitabine alone intraperitoneally, (3) radiotherapy alone, and (4) control. Tumor mass was compared at the end of the study. Compared to the control, in all study groups curcumin was found to inhibit the growth of tumors in mice and to enhance the effects of both gemcitabine therapy and radiation therapy.

This well-performed study provides an elegant mechanistic explanation for the anticancer effect of curcumin, which appears to act in a p53 independent manner. These exciting data suggest that this dietary supplement should be studied in combination with traditional forms of chemotherapy or radiotherapy in tumors dependent on the MDM2 pathway.

Mao Li, Zhuo Zhang, Donald L. Hill, Hui Wang, and Ruiwen Zhang

Cancer Res. 2007 Mar 1:67(5): 1988-96.

UroToday.com Prostate Cancer Section