Induction of G1 Cell Cycle Arrest in Human Glioma Cells by Salinomycin Through Triggering ROS-Mediated DNA Damage In Vitro and In Vivo.

Abstract

Chemotherapy has always been one of the most effective ways in combating human glioma. However, the high metastatic potential and resistance toward standard chemotherapy severely hindered the chemotherapy outcomes. Hence, searching effective chemotherapy drugs and clarifying its mechanism are of great significance. Salinomycin an antibiotic shows novel anticancer potential against several human tumors, including human glioma, but its mechanism against human glioma cells has not been fully elucidated. In the present study, we demonstrated that salinomycin treatment time- and dose-dependently inhibited U251 and U87 cells growth. Mechanically, salinomycin-induced cell growth inhibition against human glioma was mainly achieved by induction of G1-phase arrest via triggering reactive oxide species (ROS)-mediated DNA damage, as convinced by the activation of histone, p53, p21 and p27. Furthermore, inhibition of ROS accumulation effectively attenuated salinomycin-induced DNA damage and G1 cell cycle arrest, and eventually reversed salinomycin-induced cytotoxicity. Importantly, salinomycin treatment also significantly inhibited the U251 tumor xenograft growth in vivo through triggering DNA damage-mediated cell cycle arrest with involvement of inhibiting cell proliferation and angiogenesis. The results above validated the potential of salinomycin-based chemotherapy against human glioma.

• Authors: Shi-Jun Zhao, Xian-Jun Wang, Qing-Jian Wu, Chao Liu, Da-Wei Li, Xiao-Ting Fu, Hui-Fang Zhang, Lu-Rong Shao, Jing-Yi Sun, Bao-Liang Sun, Jing Zhai, Cun-Dong Fan
• Journal: Neurochemical research (Neurochem Res) Vol. 42 Issue 4 Pg. 997-1005 (Apr 2017) ISSN: 1573-6903 [Electronic] United States
• PMID: 27995497 (Publication Type: Journal Article)

Chemical References

• Pyrans
• Reactive Oxygen Species
• salinomycin

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• DNA Damage (drug effects, physiology)
• Dose-Response Relationship, Drug
• G1 Phase Cell Cycle Checkpoints (drug effects, physiology)
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Male
• Mice
• Mice, Nude
• Pyrans (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Xenograft Model Antitumor Assays (methods)