title: Realgar transforming solution displays anticancer potential against human hepatocellular carcinoma HepG2 cells by inducing ROS.
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.
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Song
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Ruilan
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Longhe
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Duan
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730020, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
mesh_terms: D042763:Acidithiobacillus / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001152:Arsenicals / Q000737:chemistry / Q000494:pharmacology*; D001673:Biodegradation, Environmental; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008516:Medicine, Chinese Traditional; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013440:Sulfides / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D017382:Reactive Oxygen Species; D013440:Sulfides; C058317:arsenic disulfide