Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells.

Abstract

Autophagy is a cell survival process that represents a therapeutic target in cancer treatment. Many types of cytochalasins have been identified and some of them have been reported to interfere with the formation of the autophagosome, although only limited data are available to assess their potential effects. Therefore, in this study, we examined the effects of cytochalasins and structurally related compounds on cell survival and the regulation of autophagy in human lung A549 adenocarcinoma cells. Cytochalasin D (CD) and cytochalasin E (CE) prominently inhibited the growth of A549 cells in a dose-dependent manner. Following treatment with CE, F-actin filaments were disrupted, and the proportion of binucleated cells increased, whereas no such effects were observed with the seven other cytochalasins tested. We found that cytochalasin H (CH), CD, and especially CE could induce the up-regulation of autophagy-related protein (LC3-II) and SQSTM1/p62. Using bafilomycin A1, we demonstrated that CD, CE, and CH inhibited autophagosome turnover, resulting in a dysfunctional autophagic process. The results of this study reveal that CE is the most potent cytochalasin in terms of its ability to induce cell death and inhibit autophagy. CE may therefore be an effective therapeutic agent against lung cancer.

• Authors: Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Sone, Shimpei Uraguchi, Keisuke Kobayashi, Hiroshi Tomoda, Masako Kiyono
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 494 Issue 3-4 Pg. 641-647 (12 16 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 29106958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cytochalasins

Topics

• A549 Cells
• Antineoplastic Agents (administration & dosage, classification)
• Autophagy (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Cytochalasins (administration & dosage, classification)
• Dose-Response Relationship, Drug