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5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells.

Authors
Type
Published Article
Journal
Oncology Reports
1021-335X
Publisher
Spandidos Publications
Publication Date
Volume
22
Issue
6
Pages
1533–1537
Identifiers
PMID: 19885610
Source
Medline

Abstract

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 microM. 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 microM), 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 microM exerted a pro-apoptotic effect via the inhibition of Akt expression. Taken together, our results suggest that 5-fluorouracil acts synergistically with apigenin inhibiting cell growth and inducing apoptosis via the down-regulation of ErbB2 expression and Akt signaling.

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