Effects of alisol B 23-acetate on ovarian cancer cells: G1 phase cell cycle arrest, apoptosis, migration and invasion inhibition

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• 作者：Le-Le Zhang^a ; Yu-Lian Xu^a ; Zheng-Hai Tang^a ; Xiao-Huang Xu^a ; Xin Chen^a ; Ting Li^a ; Chun-Yong Ding^b ; Ming-Qing Huang^c ; Xiu-Ping Chen^a ; Yi-Tao Wang^a ; Xiao-Feng Yuan^d ; ^{sjyxf.ok@163.com" class="auth_mail" title="E-mail the corresponding author} ; Jin-Jian Lu^a ; ^{jinjianlu@umac.mo" class="auth_mail" title="E-mail the corresponding author} ; ^{jinjian.lu@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ovarian cancer ; Alisol B 23-acetate ; Cell cycle arrest ; Apoptosis ; Migration ; Invasion
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：23
• 期：8
• 页码：800-809
• 全文大小：4179 K

文摘

Ovarian cancer is the first leading cause of death among gynecologic malignancies worldwide. Discovery of new chemotherapeutic drugs is still imperative for the improvement of the survival rate.

Purpose

This study aims to investigate the anti-cancer potential of alisol B 23-acetate (AB23), a protostane-type triterpene isolated from the Alismatis Rhizoma, in the parental and paclitaxel-resistant ovarian cancer cells.

Methods

MTT assay was performed to evaluate cell viability after treatment with AB23, along with flow cytometry for apoptosis and cell cycle analysis. Western blotting was conducted to determine the relative protein level. Wound healing and transwell assays were performed to investigate the effect of AB23 on cell migration and invasion.

Results

AB23 obviously inhibited proliferation of the three ovarian cancer cell lines, down-regulated the protein levels of CDK4, CDK6, and cyclin D1, and blocked the cell cycle progressions in G1 phase. Meanwhile, AB23 induced accumulation of the sub-G1 phase in the three cell lines in a concentration dependent manner. The protein levels of cleaved poly ADP-ribose polymerase (PARP) and the ratio of Bax/Bcl-2 were up-regulated after treatment with AB23. Further study showed that AB23 induced endoplasmic reticulum stress through IRE1 signaling pathway and silencing of IRE1α partially enhanced AB23-induced apoptosis. Wound healing and transwell assays showed that AB23 could also suppress the migration and invasion of HEY cells. Moreover, it down-regulated the protein levels of matrix metalloproteinases MMP-2 and MMP-9.

Conclusion

AB23 possessed anti-proliferation, anti-migration and anti-invasion activities as a single agent on ovarian cancer cells.