title: Caudatin Inhibits Human Glioma Cells Growth Through Triggering DNA Damage-Mediated Cell Cycle Arrest.
abstract: Caudatin, one of the species of C-21 steroidal glycosides mainly isolated from the root of Cynanchum bungei Decne, exhibits potent anticancer activities. However, the mechanism remains poorly defined. In the present study, the growth inhibitory effect and mechanism of caudatin on human glioma cells were evaluated in vitro. The results revealed that caudatin time- and dose-dependently inhibited U251 and U87 cells growth. Flow cytometry analysis indicated that caudatin-induced growth inhibition against U251 and U87 cells was mainly achieved by the induction of G0/G1 and S-phase cell cycle arrest through triggering DNA damage, as convinced by the up-regulation of p53, p21, and histone phosphorylation, as well as the down-regulation of cyclin D1. Moreover, caudatin treatment also triggered the activation of ERK and inactivation of AKT pathway. LY294002 (an AKT inhibitor) addition enhanced caudation-induced AKT inhibition, indicating that caudatin inhibited U251 cells growth in an AKT-dependent manner. Taken together, these results indicate that caudatin may act as a novel cytostatic reagent against human glioma cells through the induction of DNA damage-mediated cell cycle arrest with the involvement of modulating MAPK and AKT pathways.
authors: Department of Chemistry, Jinan University, Guangzhou, 510632, China. tsmc_nks@tsmc.edu.cn.|School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China. tsmc_nks@tsmc.edu.cn.|Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. tsmc_nks@tsmc.edu.cn.
authors: Xiao-yan
authors: XY
authors: Fu
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Shuai
authors: S
authors: Zhang
authors: Taishan Vocational College of Nursing, Taian, 271000, Shandong, China.
authors: Kun
authors: K
authors: Wang
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Ming-feng
authors: MF
authors: Yang
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. cdfan@tsmc.edu.cn.
authors: Cun-dong
authors: CD
authors: Fan
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. blsun88@163.com.|Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. blsun88@163.com.
authors: Bao-liang
authors: BL
authors: Sun
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006027:Glycosides; D006131:Growth Inhibitors; D013256:Steroids; C570806:caudatin
keywords: Apoptosis; Caudatin; Cell cycle arrest; DNA damage; Glioma cell; MAPK