Fangchinoline inhibits cell proliferation via Akt/GSK-3beta/ cyclin D1 signaling and induces apoptosis in MDA-MB-231 breast cancer cells.

Abstract

Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.

• Authors: Chang-Dong Wang, Cheng-Fu Yuan, You-Quan Bu, Xiang-Mei Wu, Jin-Yuan Wan, Li Zhang, Ning Hu, Xian-Jun Liu, Yong Zu, Ge-Li Liu, Fang-Zhou Song
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 2 Pg. 769-73 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 24568493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzylisoquinolines
• CCND1 protein, human
• RNA, Messenger
• Cyclin D1
• fangchinoline
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3

Topics

• Apoptosis (drug effects)
• Benzylisoquinolines (pharmacology)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D1 (genetics, metabolism)
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured