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毛柿素通过抑制组蛋白去乙酰化酶3在体外和体内抑制乳腺癌。

Moscatilin Suppresses the Breast Cancer Both In Vitro and In Vivo by Inhibiting HDAC3.

作者信息

Su Wenjie, Zeng Lianfu, Chen Weida

机构信息

Department of Tumor Surgery, Quanzhou Guangqian Hospital, Meishan Town, Nan'an City, Quanzhou, Fujian, China.

出版信息

Dose Response. 2021 Mar 15;19(1):15593258211001251. doi: 10.1177/15593258211001251. eCollection 2021 Jan-Mar.

Abstract

Moscatilin, a natural compound isolated from the orchid , has multiple pharmacological actions. The present study investigated the anti-tumor role of moscatilin in breast cancer and elucidated the underlying mechanisms. Cell proliferation, viability, and apoptosis of moscatilin treated MDA-MB-231 cells were determined by CCK-8 assay and flow cytometry. Histone deacetylases (HDACs) expression levels and global acetylated status of breast cancer cells were detected by Western blot and qPCR. Mouse xenograft model was established to evaluate the anti-cancer effects of moscatilin. Moscatilin treatment dose dependently suppressed proliferation and increased apoptosis of breast cancer cells. Moreover, moscatilin administration dramatically repressed tumor growth and extended survival time of mouse model. Mechanistically, moscatilin down-regulated HDAC3 expression, and then enhanced the global acetylated status of histone H3 (H3K9Ac) and H4 (H4K16Ac). Our findings indicate that moscatilin can inhibit the proliferation and promote apoptosis of breast cancer in vitro and in vivo, which suggests that moscatilin can be used as a potential therapeutic agent for the treatment of breast cancer.

摘要

从兰花中分离出的天然化合物毛麝香亭具有多种药理作用。本研究调查了毛麝香亭在乳腺癌中的抗肿瘤作用,并阐明了其潜在机制。通过CCK-8法和流式细胞术测定毛麝香亭处理的MDA-MB-231细胞的细胞增殖、活力和凋亡情况。通过蛋白质免疫印迹法和定量聚合酶链反应检测乳腺癌细胞中组蛋白去乙酰化酶(HDACs)的表达水平和整体乙酰化状态。建立小鼠异种移植模型以评估毛麝香亭的抗癌效果。毛麝香亭处理以剂量依赖性方式抑制乳腺癌细胞的增殖并增加其凋亡。此外,给予毛麝香亭可显著抑制小鼠模型的肿瘤生长并延长其生存时间。机制上,毛麝香亭下调HDAC3的表达,进而增强组蛋白H3(H3K9Ac)和H4(H4K16Ac)的整体乙酰化状态。我们的研究结果表明,毛麝香亭在体外和体内均可抑制乳腺癌细胞的增殖并促进其凋亡,这表明毛麝香亭可作为治疗乳腺癌的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d660/7968028/5ee8da11f1a7/10.1177_15593258211001251-fig1.jpg

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