School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Eur J Pharmacol. 2020 May 5;874:172990. doi: 10.1016/j.ejphar.2020.172990. Epub 2020 Feb 11.
Ovarian carcinoma (OC) begins in the ovaries and remains a highly lethal malignancy. Despite great efforts have been made to fight against OC, there still remain limited therapeutic options owing to chemotherapy drug resistance and serious side effects. Osthole is a derivative of coumarin and extracted from Cnidium monnieri (L.) Cusson, which has been drawn more attention due to its high biological activity in various disease. However, the underlying mechanism of osthole in OC is still unclear. In this study, we aim to evaluate the mechanism of osthole against OC cells. Methodologically, Cell Counting Kit-8 (CCK-8) and LIVE/DEAD™ Cell Imaging experiments were employed to assess cell viability. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) staining, flow cytometry, Hoechst staining, JC-1 staining assay and western blotting were performed to study apoptosis. Transmission electron microscopy, western blotting and monodansyl cadaverine (MDC) staining assay were used to study autophagy. Western blotting and microscopy image were employed to determine pyroptosis. Our results demonstrated that osthole could significantly suppress OC cells growth in a dose-dependent manner. We further proved that osthole could inhibit OC cells growth by mitochondria-mediated apoptosis. Meanwhile, we also discovered that osthole could trigger cell autophagy and lead to cell death. Furthermore, our study revealed that osthole could lead to pyroptosis through inducing the cleavage of gasdermin E (c-GSDME) level. Taken together, Osthole could significantly suppress the growth of OC cells and induce OC cells death via apoptosis, pyroptosis and autophagy, which is a promising new drug for the treatment of OC.
卵巢癌（OC）起源于卵巢，仍是一种高度致命的恶性肿瘤。尽管为了对抗 OC 已经付出了巨大努力，但由于化疗药物耐药性和严重的副作用，治疗选择仍然有限。蛇床子素是香豆素的衍生物，从蛇床子（Cnidium monnieri（L.）Cusson）中提取，由于其在各种疾病中的高生物活性而受到更多关注。然而，蛇床子素在 OC 中的作用机制尚不清楚。在这项研究中，我们旨在评估蛇床子素对 OC 细胞的作用机制。在方法上，采用细胞计数试剂盒（CCK-8）和 LIVE/DEAD™细胞成像实验来评估细胞活力。2'，7'-二氯荧光素二乙酸酯（DCFH-DA）染色、流式细胞术、Hoechst 染色、JC-1 染色实验和 Western blot 用于研究细胞凋亡。透射电子显微镜、Western blot 和单丹磺酰尸胺（MDC）染色实验用于研究自噬。Western blot 和显微镜图像用于确定细胞焦亡。我们的结果表明，蛇床子素可以显著抑制 OC 细胞的生长，呈剂量依赖性。我们进一步证明，蛇床子素通过线粒体介导的细胞凋亡抑制 OC 细胞的生长。同时，我们还发现蛇床子素可以触发细胞自噬并导致细胞死亡。此外，我们的研究表明，蛇床子素通过诱导天冬氨酸特异性半胱氨酸蛋白酶 1（caspase-1）依赖性 Gasdermin E（c-GSDME）的裂解，导致细胞焦亡。总之，蛇床子素可以显著抑制 OC 细胞的生长，并通过细胞凋亡、细胞焦亡和自噬诱导 OC 细胞死亡，是治疗 OC 的一种有前途的新药。
