title: Attenuation of Cisplatin-Induced Neurotoxicity by Cyanidin, a Natural Inhibitor of ROS-Mediated Apoptosis in PC12 Cells.
abstract: Cisplatin-based chemotherapy in clinic is severely limited by its adverse effect, including neurotoxicity. Oxidative damage contributes to cisplatin-induced neurotoxicity, but the mechanism remains unclearly. Cyanidin, a natural flavonoid compound, exhibits powerful antioxidant activity. Hence, we investigated the protective effects of cyanidin on PC12 cells against cisplatin-induced neurotoxicity and explored the underlying mechanisms. The results showed that cisplatin-induced cytotoxicity was completely reversed by cyanidin through inhibition of PC12 cell apoptosis, as proved by the attenuation of Sub-G1 peak, PARP cleavage, and caspases-3 activation. Mechanistically, cyanidin significantly inhibited reactive oxygen species (ROS)-induced DNA damage in cisplatin-treated PC12 cells. Our findings revealed that cyanidin as an apoptotic inhibitor effectively blocked cisplatin-induced neurotoxicity through inhibition of ROS-mediated DNA damage and apoptosis, predicating its therapeutic potential in prevention of chemotherapy-induced neurotoxicity. Cisplatin caused DNA damage, activated p53, and subsequently induced PC12 cells apoptosis by triggering ROS overproduction. However, cyanidin administration effectively inhibited DNA damage, attenuated p53 phosphorylation, and eventually reversed cisplatin-induced PC12 cell apoptosis through inhibition ROS accumulation.
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, Jinan, 250014, Shandong, China.|Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Jing-yi
authors.initials: JY
authors.lastname: Sun
authors.affiliation: Taishan Vocational College of Nursing, Taian, 271000, Shandong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Hou
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Ming-feng
authors.initials: MF
authors.lastname: Yang
authors.affiliation: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Zong-yong
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Lei-lei
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. tsmc_nks@tsmc.edu.cn.
authors.forename: Cun-dong
authors.initials: CD
authors.lastname: Fan
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, Jinan, 250014, Shandong, China. zhumeijia1818@163.com.
authors.forename: Mei-jia
authors.initials: MJ
authors.lastname: Zhu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. blsun@tsmc.edu.cn.|Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. blsun@tsmc.edu.cn.
authors.forename: Bao-liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D017382:Reactive Oxygen Species; C017154:cyanidin; D002945:Cisplatin
keywords: Apoptosis; Cisplatin; Cyanidin; Neurotoxicity; Reactive oxygen species