Realgar transforming solution displays anticancer potential against human hepatocellular carcinoma HepG2 cells by inducing ROS

Song,Peng; Chen,Peng; Wang,Dong; Wu,Zhengrong; Gao,Qiyu; Wang,Aixia; Zhu,Ruilan; Wang,Yajun; Wang,Xin; Zhao,Longhe; Duan,Ziyun; Zhu,Shuqian; Cui,Peng; Li,Yang; Li,Hongyu

doi:10.3892/ijo.2016.3831

Realgar transforming solution displays anticancer potential against human hepatocellular carcinoma HepG2 cells by inducing ROS

Authors:
- Peng Song
- Peng Chen
- Dong Wang
- Zhengrong Wu
- Qiyu Gao
- Aixia Wang
- Ruilan Zhu
- Yajun Wang
- Xin Wang
- Longhe Zhao
- Ziyun Duan
- Shuqian Zhu
- Peng Cui
- Yang Li
- Hongyu Li
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Affiliations: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China
Published online on: December 30, 2016 https://doi.org/10.3892/ijo.2016.3831
Pages: 660-670

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Abstract

Realgar (As4S4), as a mineral drug containing arsenic compound, has been employed in clinical therapy of cancer for its good therapeutic reputation in Chinese traditional medicine. However, large dose of realgar and long period of treatment are necessary for achieving the effective blood medicine concentration due to its low bioavailability resulted from poor solubility. In this study, we obtained realgar transforming solution (RTS) using intrinsic biotransformation in microorganism, and investigated underlying mechanisms of RTS for HepG2 cells. Our results demonstrated that an effective biotransformation of realgar method by A. ferrooxidans was established, in which realgar was biologically converted into an aqueous solution, and RTS had a strong activity inducing apoptosis and interrupting G2/M progression in HepG2 cells via upregulation of cellular ROS. Importantly, RTS inhibited the cellular antioxidant defense system leading to abundant ROS accumulation, and activated cell cycle arrest and mitochondrial pathway of apoptosis mediated by activating p53 due to cellular uncontrolled ROS. Collectively, our findings suggest that RTS is a potential candidate for therapy of human hepatocellular carcinoma.

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