Abstract #5116: 5-Fluorouracil Combined with Apigenin Enhances Anticancer Activity Through Induction of Apoptosis in Human Breast Cancer MDA-MB-453 Cells

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO We investigated the effects of combined treatment with 5-fluorouracil and apigenin on proliferation and apoptosis, as well as the underlying mechanism, in human breast cancer MDA-MB-453 cells. The MDA-MB-453 cells, which have been shown to overexpress ErbB2, were resistant to 5-fluorouracil; 5-fluorouracil exhibited a small dose-dependent anti-proliferative effect, with an IC50 of 90 \#956;M. Interestingly, combined treatment with apigenin significantly decreased the resistance. Cellular proliferation was significantly inhibited in cells exposed to 5-fluorouracil at its IC50 and apigenin (5, 10, 50, and 100 \#956;M), compared with proliferation in cells exposed to 5-fluorouracil alone. This inhibition in turn led to apoptosis, as evidenced by an increased number of apoptotic cells and the activation of caspase-3. To investigate the mechanism by which the combination of 5-fluorouracil and apigenin induces apoptosis, ErbB2 expression was analyzed. The level of ErbB2 was unchanged by 5-fluorouracil alone but was drastically reduced in cells treated with 5-fluorouracil plus apigenin. Moreover, compared with 5-fluorouracil alone, 5-fluorouracil in combination with apigenin at concentrations >10 \#956;M exerted a pro-apoptotic effect via the inhibition of Akt expression. Taken together, our results suggest that 5-fluorouracil acts synergistically with apigenin to inhibit cell growth and to induce apoptosis via the downregulation of ErbB2 expression and Akt signaling. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5116.