Hye-Sook Seo1, Jin Mo Ku1, Han-Seok Choi1, Jong-Kyu Woo2, Bo-Hyoung Jang1, Yong Cheol Shin1, Seong-Gyu Ko3. 1. Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea. 2. College of Pharmacy, Gachon University of Medicine and Science, Yeonsu-gu, Incheon, Republic of Korea. 3. Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea epiko@khu.ac.kr.
Abstract
BACKGROUND: This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells. MATERIALS AND METHODS: The antiproliferative effects of apigenin were examined by proliferation and MTT assays. The effect of apigenin on apoptotic molecules was determined by western blotting. RT-PCR was performed to measure mRNA levels of HIF-1α and VEGF. ELISA assay was performed to measure intracellular VEGF levels. Immunocytochemistry was performed to evaluate nuclear STAT3 level. RESULTS: Apigenin inhibited the proliferation of MDA-MB-453 cells. Apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP. Apigenin induced extrinsic apoptosis and blocked the activation (phosphorylation) of JAK2 and STAT3. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear staining of STAT3. CONCLUSION: Apigenin exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer. Copyright
BACKGROUND: This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells. MATERIALS AND METHODS: The antiproliferative effects of apigenin were examined by proliferation and MTT assays. The effect of apigenin on apoptotic molecules was determined by western blotting. RT-PCR was performed to measure mRNA levels of HIF-1α and VEGF. ELISA assay was performed to measure intracellular VEGF levels. Immunocytochemistry was performed to evaluate nuclear STAT3 level. RESULTS: Apigenin inhibited the proliferation of MDA-MB-453 cells. Apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP. Apigenin induced extrinsic apoptosis and blocked the activation (phosphorylation) of JAK2 and STAT3. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear staining of STAT3. CONCLUSION: Apigenin exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer. Copyright