Resveratrol and curcumin are both effective in inhibiting the growth of colon cancer cells

Author Block:	Bhaumik B. Patel, Deep-Shikha Gupta, Vivek Sengupta, Adhip PN Majumdar. VAMC/ Wayne State University, Farmington Hills, MI, Wayne State University, Detroit, MI, VAMC/ Wayne State University, Detroit, MI
Despite recent advances in medicine, mortality from colon cancer remains unacceptably high. 5-fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces incomplete response resulting in survival of cells (Chemo-surviving cells) that often leads to cancer recurrence. Thus, validation of a non-toxic chemopreventative agent that could prevent the recurrence of colorectal cancer would be highly desirable. Curcumin (diferuloylmethane; the yellow pigment of turmeric used in South Asian cuisine) and resveratrol (trans-3,5,4'-trihydroxystilben; found in many plant species, including peanuts and grapes), with no discernible toxicity, are known to inhibit initiation, promotion and progression of carcinogenesis. The present investigation was, therefore, undertaken to examine whether addition of curcumin or resveratrol to FOLFOX will be a superior therapeutic strategy for chemo-surviving cells. Forty-eight-hour treatment of colon cancer HCT-116 or HT-29 cells with FOLFOX (25 mM 5-FU+0.625 mM oxaliplatin) resulted in 60-70% cell survival, accompanied by a marked activation of IGF-1R and minor to moderate increase in EGFR, HER-2 as well as AKT, COX-2 and Cyclin-D1. However, inclusion of resveratrol or curcumin to continued FOLFOX treatment for another 48 h greatly decreased the survival of these cells, compared to those subjected or not subjected to continued FOLFOX treatment (control). Moreover, our studies demonstrate that while resveratrol and curcumin are both effective in inhibiting the growth of colon cancer HCT-116 and HT-29 cells, curcumin appears to be superior in this respect. These changes are associated with concomitant reduction in expression and activation of EGFR, HER-2 as well as IGF-1R. Additionally, expression of down-stream signaling effectors such as AKT, COX-2 and Cyclin-D1 was down-regulated in a similar fashion. In conclusion, our data suggest that inclusion of curcumin or resveratrol to conventional chemotherapeutic regimen could be one of the effective strategy to prevent the emergence of chemo-resistant colon cancer cells.

2008 AACR Annual Meeting
April 12-16, 2008
San Diego, CA
tag: Cancer, Cancer treatment, resveratrol, curcumin, 2008 AACR Annual Meeting, FOLFOX treatment, colon cancer, colorectal cancer chemotherapeutics, Chemo-surviving cells