Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation

Li, Xinxing, Wang, Haolu, Wang, Juan, Chen, Yuying, Yin, Xiaobin, Shi, Guiying, Li, Hui, Hu, Zhiqian and Liang, Xiaowen (2016) Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation. Bmc Cancer, 16 1: . doi:10.1186/s12885-016-2640-3


Author Li, Xinxing
Wang, Haolu
Wang, Juan
Chen, Yuying
Yin, Xiaobin
Shi, Guiying
Li, Hui
Hu, Zhiqian
Liang, Xiaowen
Title Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation
Journal name Bmc Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2016-08-02
Sub-type Article (original research)
DOI 10.1186/s12885-016-2640-3
Open Access Status DOI
Volume 16
Issue 1
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 2730 Oncology
1311 Genetics
1306 Cancer Research
Abstract Background: Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells. Methods: Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination. Results: Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity. Conclusions: This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.
Formatted abstract
Background: Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells.

Methods: Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination.

Results: Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/ cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity.

Conclusions: This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.
Keyword Bladder cancer
Emodin
Cisplatin
ROS
MRP1
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 81402002
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Admin Only - School of Medicine
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Sep 2016, 10:24:46 EST by System User on behalf of Learning and Research Services (UQ Library)