Germacrone Regulates HBXIP-Mediated Cell Cycle, Apoptosis and Promotes the Formation of Autophagosomes to Inhibit the Proliferation of Gastric Cancer Cells.
Germacrone Regulates HBXIP-Mediated Cell Cycle, Apoptosis and Promotes the Formation of Autophagosomes to Inhibit the Proliferation of Gastric Cancer Cells.
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Germacrone 调节 HBXIP 介导的细胞周期、细胞凋亡并促进自噬体形成抑制胃癌细胞增殖
DOI：
10.3389/fonc.2020.537322
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发表时间：
2020
影响因子：
4.7
通讯作者：
Xia Q
中科院分区：
文献类型：
--
作者：
Fang X;Tan T;Gao B;Zhao Y;Liu T;Xia Q
Germacrone是一种单环倍半萜类化合物，在多种癌症中具有显著的抗肿瘤作用，包括肝细胞癌、胃癌和乳腺癌。然而，吉马酮对胃癌的作用机制尚不清楚。在这项研究中，我们发现吉马酮以剂量依赖的方式抑制胃癌细胞的增殖，并诱导这些细胞的G0/G1期细胞周期停滞和凋亡。此外，吉马酮还增加了LC3II/LC3I的表达。与吉马酮和巴菲霉素A1(Baf A1)处理组相比，吉马酮处理组的LC3II/LC3I值显著增加，提示吉马酮促进自噬小体的形成。然后用蛋白质组学分析确定吉马酮在胃癌中的分子靶点。共筛选出596个蛋白质，其中最重要的是晚期内体/溶酶体适配子和MAPK和MTOR激活剂5(LAMTOR5，也称为HBXIP)。HBXIP的过表达延迟了吉马酮诱导的细胞周期停滞、细胞凋亡的诱导和自噬的抑制。综上所述，我们的结果表明吉马酮通过抑制HBXIP抑制胃癌细胞的增殖，这一过程与G0/G1期停滞和细胞凋亡有关。
Germacrone, a monocyclic sesquiterpene, exerts marked antitumor effects in a variety of cancers, including hepatocellular carcinoma, gastric cancer, and breast cancer. However, the mechanism underlying the effects of germacrone on gastric cancer remains unclear. In this study, we show that germacrone inhibited gastric cancer cell proliferation in a dose-dependent manner, and induced G0/G1-phase cell cycle arrest and apoptosis in these cells. Moreover, germacrone increased the expression of LC3II/LC3I. And LC3II/LC3I was significant increased after germacrone treatment compared with germacrone and bafilomycin A1 (Baf A1) treatment, which suggested germacrone promoted the formation of autophagosomes. Proteomic analysis was then used to identify molecular targets of germacrone in gastric cancer. A total of 596 proteins were screened, and the top hit was identified as late endosomal/lysosomal adaptor and MAPK and MTOR activator 5 (LAMTOR5, also named HBXIP). Overexpression of HBXIP delayed the germacrone-induced cell cycle arrest, induction of apoptosis, and inhibition of autophagy. Combined, our results indicate that germacrone suppresses gastric cancer cell proliferation by inhibiting HBXIP, and this process is related to G0/G1-phase arrest and apoptosis.
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