title: Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells.
abstract: BACKGROUND
  This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells.
  
  
  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.
  
  
  CONCLUSIONS
  Apigenin exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer.
authors.affiliation: 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.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Seo
authors.affiliation: 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.
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Ku
authors.affiliation: 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.
authors.forename: Han-Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Gachon University of Medicine and Science, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Jong-Kyu
authors.initials: JK
authors.lastname: Woo
authors.affiliation: 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.
authors.forename: Bo-Hyoung
authors.initials: BH
authors.lastname: Jang
authors.affiliation: 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.
authors.forename: Yong Cheol
authors.initials: YC
authors.lastname: Shin
authors.affiliation: 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.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D047310:Apigenin; D020169:Caspases; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C494086:STAT3 protein, human; C467484:VEGFA protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; STAT3; VEGF; apigenin; apotosis