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Cantharidin downregulates PSD1 expression and inhibits autophagic flux in yeast cells

机译:斑蝥素下调酵母细胞中 PSD1 表达并抑制自噬通量

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摘要

Cantharidin is a terpenoid compound of insect origin, naturally produced by male blister beetles as an antipredatory mechanism. Cantharidin has anticancer properties, which are attributed to its ability to induce cell cycle arrest, DNA damage, MAPK signaling pathway, and apoptosis. Cantharidin has been reported to induce apoptosis in triple-negative breast cancer cells by suppressing autophagy via downregulation of Beclin 1 expression and autophagosome formation. However, it remains unclear which stage of the autophagic pathway is targeted by cantharidin. Herein, we report that yeast cells are sensitive to cantharidin, and external supplementation of ethanolamine (ETA) ameliorates the cytotoxicity. In addition, cantharidin downregulates phosphatidylserine decarboxylase 1 (PSD1) expression. We also report that cantharidin inhibits autophagic flux, and external administration of ETA could rescue this inhibition. Additionally, cotreatment with chloroquine sensitized the autophagy inhibitory effects of cantharidin. We conclude that yeast cells are sensitive to cantharidin due to inhibition of autophagic flux.
机译:斑蝥素是一种昆虫来源的萜类化合物,由雄性水泡甲虫作为抗捕食机制自然产生。斑蝥素具有抗癌特性,这归因于其诱导细胞周期停滞、DNA 损伤、MAPK 信号通路和细胞凋亡的能力。据报道,斑蝥素通过下调 Beclin 1 表达和自噬体形成抑制自噬,从而诱导三阴性乳腺癌细胞凋亡。然而,目前尚不清楚斑蝥素靶向自噬途径的哪个阶段。在此,我们报道酵母细胞对斑蝥素敏感,并且外部补充乙醇胺 (ETA) 可改善细胞毒性。此外,斑蝥素下调磷脂酰丝氨酸脱羧酶 1 (PSD1) 的表达。我们还报道了斑蝥素抑制自噬通量,外用ETA可以挽救这种抑制。此外,与氯喹共处理使斑蝥素的自噬抑制作用敏感。我们得出结论,由于抑制自噬通量,酵母细胞对斑蝥素敏感。

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