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


OBJECTIVE
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.


CONCLUSIONS
AB23 possessed anti-proliferation, anti-migration and anti-invasion activities as a single agent on ovarian cancer cells.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Le-Le
LL
Zhang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Yu-Lian
YL
Xu
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Zheng-Hai
ZH
Tang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Xiao-Huang
XH
Xu
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Xin
X
Chen
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Ting
T
Li
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chun-Yong
CY
Ding
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Ming-Qing
MQ
Huang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Xiu-Ping
XP
Chen
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Yi-Tao
YT
Wang
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: sjyxf.ok@163.com.
Xiao-Feng
XF
Yuan
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: jinjianlu@umac.mo.
Jin-Jian
JJ
Lu
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002783:Cholestenones / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D002783:Cholestenones; D009363:Neoplasm Proteins; C526957:alisol B 23-acetate
Alisol B 23-acetate; Apoptosis; Cell cycle arrest; Invasion; Migration; Ovarian cancer