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, fluorescenceactivated cell sorting analysis, western blot analysis, immunocytochemistry, reverse transcriptionpolymerase 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 timedependent manner. This inhibition of growth was accompanied by an increase in the subG0/G1 apoptotic population. Furthermore, apigenin enhanced the expression levels of cleaved caspase8
and 3, and induced the cleavage of poly(adenosine diphosphate ribose) polymerase in SKBR3 cells, confirming that apigenin promotes apoptosis via a caspasedependent pathway. Apigenin additionally reduced the expression of phosphorylated (p)janus kinase 2 and psignal transducer and
activator of transcription 3 (STAT3), inhibited CoCl2induced vascular endothelial growth factor (VEGF) secretion and decreased the nuclear localization of STAT3. The STAT3 inhibitor S31201 decreased the cellular proliferation rate and reduced the expression of pSTAT3 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.
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Document Type: Research Article
Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, College of Korean Medicine, Kyung Hee University, Dongdaemungu, Seoul 130701, Republic of Korea
College of Pharmacy, Gachon University of Medicine and Science, Yeonsugu, Incheon 406840, Republic of Korea
Department of Oriental Medicine, Semyung University, College of Korean Medicine, Jecheon, Chungbuk 390711, Republic of Korea
Publication date: August 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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