The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

Chih Chuan Teng, Hsing Chun Kuo, Ho Chen Cheng, Ting Chung Wang, Chun-I Sze

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr 15 and Cdc25cSer 216. Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer 216 expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer 216 in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer 216 cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalToxicology and Applied Pharmacology
Volume263
Issue number1
DOIs
Publication statusPublished - 2012 Aug 15

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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