[논문]Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells

Takanezawa, Yasukazu; Nakamura, Ryosuke; Sone, Yuka; Uraguchi, Shimpei; Kobayashi, Keisuke; Tomoda, Hiroshi; Kiyono, Masako

doi:10.1016/j.bbrc.2017.10.135

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

Biochemical and biophysical research communications, v.494 no.3/4, 2017년, pp.641 - 647

Takanezawa, Yasukazu (Department of Public Health, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Nakamura, Ryosuke (Department of Public Health, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Sone, Yuka (Department of Public Health, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Uraguchi, Shimpei (Department of Public Health, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Kobayashi, Keisuke (Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Tomoda, Hiroshi (Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan) , Kiyono, Masako (Department of Public Health, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan)

Abstract ▼ AI-Helper

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. Highlights Cytochalasin E and H are novel inhibitors of autophgic flux. Cytochalasin D, E, and H inhibit autophagy and are new anti-cancer drug candidates. Phenochalasin A inhibits lipid droplet formation without autophagic effects.

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

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