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

Abstract

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-G0/G1 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.

• Authors: Hye-Sook Seo, Jin Mo Ku, Han-Seok Choi, Jong-Kyu Woo, Bo-Hyoung Jang, Hoyeon Go, Yong Cheol Shin, Seong-Gyu Ko
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 2 Pg. 2977-84 (Aug 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25936427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• STAT3 Transcription Factor
• Vascular Endothelial Growth Factor A
• Cobalt
• Apigenin
• Poly(ADP-ribose) Polymerases
• ERBB2 protein, human
• Receptor, ErbB-2
• JAK2 protein, human
• Janus Kinase 2
• Caspase 3
• Caspase 8
• Caspases
• cobaltous chloride

Topics

• Apigenin (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cobalt (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Female
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Immunohistochemistry
• Janus Kinase 2
• Phosphorylation (drug effects)
• Poly(ADP-ribose) Polymerases (metabolism)
• Receptor, ErbB-2 (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (analysis, metabolism)