Dynasore suppresses proliferation and induces apoptosis of the non-small-cell lung cancer cell line A549.

Abstract

Lung cancer is the leading cause of cancer death worldwide, and most of all cases are non-small-cell lung cancer. Lung cancer is associated with dysregulation of mitochondrial fusion and fission, and inhibition of the fission regulator Dynamin-related protein 1 (Drp1) reduces proliferation and increases apoptosis of lung cancer cells. Dynasore is a small molecule non-selective inhibitor of the GTPase activity of dynamin 1, dynamin 2, and Drp1 in vivo and in vitro. Here, we investigated the effects of dynasore on the proliferation and apoptosis of A549 lung cancer cells, alone and in combination with the chemotherapeutic drug cisplatin. We found that cisplatin increased mitochondrial fission and dynamin 2 expression, whereas dynasore had the opposite effects. However, both cisplatin and dynasore independently induced mitochondrial oxidative stress, leading to mitochondrial dysfunction, reduced cell proliferation, and enhanced apoptosis. Importantly, dynasore significantly augmented the anti-cancer effects of cisplatin. To the best of our knowledge, this is the first report that dynasore inhibits proliferation and induces apoptosis of lung cancer cells, and enhances the inhibitory effects of cisplatin.

• Authors: Feifei Shen, Junda Gai, Jilin Xing, Jingqian Guan, Lin Fu, Qingchang Li
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 495 Issue 1 Pg. 1158-1166 (01 01 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 29175207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydrazones
• N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
• Cisplatin

Topics

• A549 Cells
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cisplatin (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Synergism
• Humans
• Hydrazones (administration & dosage)
• Lung Neoplasms (drug therapy, metabolism, pathology)