Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells

被引:59
作者
Seo, Hye-Sook [1 ,2 ]
Ku, Jin Mo [1 ,2 ]
Choi, Han-Seok [1 ,2 ]
Woo, Jong-Kyu [3 ]
Jang, Bo-Hyoung [1 ,2 ]
Go, Hoyeon [4 ]
Shin, Yong Cheol [1 ,2 ]
Ko, Seong-Gyu [1 ,2 ]
机构
[1] Kyung Hee Univ, Lab Clin Biol & Pharmacogen, Seoul 130701, South Korea
[2] Kyung Hee Univ, Ctr Clin Res & Genom, Coll Korean Med, Seoul 130701, South Korea
[3] Gachon Univ Med & Sci, Coll Pharm, Inchon 406840, South Korea
[4] Semyung Univ, Dept Oriental Med, Coll Korean Med, Jecheon 390711, Chungbuk, South Korea
基金
新加坡国家研究基金会;
关键词
breast cancer; human epidermal growth factor receptor 2; apigenin; apoptosis; signal transducer and activator of transcription 3; vascular endothelial growth factor; CYCLE ARREST; VEGF EXPRESSION; STAT3; RECEPTOR; DEATH; MELANOMA; PROSTATE; SRC; PHOSPHORYLATION; INDUCTION;
D O I
10.3892/mmr.2015.3698
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Phytoestrogens have been demonstrated to inhibit tumor induction; however, their molecular mechanisms of action have remained elusive. The present study aimed to investigate the effects of a phytoestrogen, apigenin, on proliferation and apoptosis of the human epidermal growth factor receptor 2 (HER2)-expressing breast cancer cell line SKBR3. Proliferation assay, MTT assay, fluorescence-activated cell sorting analysis, western blot analysis, immunocytochemistry, reverse transcription-polymerase chain reaction and ELISA assay were used in the present study. The results of the present study indicated that apigenin inhibited the proliferation of SKBR3 cells in a dose- and time-dependent manner. This inhibition of growth was accompanied by an increase in the sub-G(0)/G(1) apoptotic population. Furthermore, apigenin enhanced the expression levels of cleaved caspase-8 and -3, and induced the cleavage of poly(adenosine diphosphate ribose) polymerase in SKBR3 cells, confirming that apigenin promotes apoptosis via a caspase-dependent pathway. Apigenin additionally reduced the expression of phosphorylated (p)-janus kinase 2 and p-signal transducer and activator of transcription 3 (STAT3), inhibited CoCl2-induced vascular endothelial growth factor (VEGF) secretion and decreased the nuclear localization of STAT3. The STAT3 inhibitor S31-201 decreased the cellular proliferation rate and reduced the expression of p-STAT3 and VEGF. Therefore, these results suggested that apigenin induced apoptosis via the inhibition of STAT3 signaling in SKBR3 cells. In conclusion, the results of the present study indicated that apigenin may be a potentially useful compound for the prevention or treatment of HER2-overexpressing breast cancer.
引用
收藏
页码:2977 / 2984
页数:8
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