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

被引:69
作者
Choi, Eun Jeong [1 ]
Kim, Gun-Hee [1 ]
机构
[1] Duksung Womens Univ, Plant Resources Res Inst, Seoul 132714, South Korea
关键词
apoptosis; Akt pathway; apigenin; ErbB2; MDA-MB-453; cells; PI3K/AKT PATHWAY; GROWTH; ACTIVATION; DEGRADATION; FLAVONOIDS; RESISTANCE; QUERCETIN; ONCOGENE; HER2/NEU; RECEPTOR;
D O I
10.3892/or_00000598
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 all IC(50) of 90 mu M. Interestingly, combined treatment with apigenin significantly decreased the resistance. Cellular proliferation was significantly inhibited in cells exposed to 5-fluorouracil at its IC(50) and apigenin (5, 10, 50 and 100 mu 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 mu M 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.
引用
收藏
页码:1533 / 1537
页数:5
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