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Combined Treatment with 5-Fluorouracil and Capsaicin Induces Apoptosis in HT-29 Human Colon Cancer Cells  

Lee, Yun-Seok (College of Pharmacy, Yeungnam University)
Lee, Jong-Suk (College of Pharmacy, Yeungnam University)
Kim, Jung-Ae (College of Pharmacy, Yeungnam University)
Publication Information
YAKHAK HOEJI / v.53, no.4, 2009 , pp. 184-188 More about this Journal
Abstract
Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.
Keywords
5-fluorouracil; capsaicin; HT-29 human colon adenocarcinoma cells; peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$); combination therapy;
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