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玫瑰茄多糖通过 PI3K/AKT/mTOR 通路诱导人宫颈癌细胞自噬介导的细胞凋亡。

Rosa rugosa polysaccharide induces autophagy-mediated apoptosis in human cervical cancer cells via the PI3K/AKT/mTOR pathway.

机构信息

College of Life Sciences, Jilin Agricultural University, Changchun 130118, Jilin, China.

Department of Animal Sciences, Shaheed Benazir Bhutto University Sheringal, Dir Upper, Pakistan.

出版信息

Int J Biol Macromol. 2022 Jul 1;212:257-274. doi: 10.1016/j.ijbiomac.2022.05.023. Epub 2022 May 6.

Abstract

The aim of this study was to investigate the effect of a polysaccharide from Rosa rugosa Thunb. on human cervical cancer cells (HCCCs) and the underlying mechanism. Here, a novel Rosa rugosa polysaccharide, named as RRP, was purified from Rosa rugosa petals. RRP consisted of glucose, galacturonic acid, mannose, rhamnose, galactose, arabinose, xylose, and glucuronic acid (molar ratio: 7.78:7.59:4.23:3.22:3.15:1.65:1.00), with Mw of 327.92 kDa. RRP remarkably inhibited cell proliferation, migration, and cell cycle arrest in HeLa and SiHa cells. Furthermore, RRP induced apoptosis by activating the caspase family of proteins and mediating the reactive oxygen species (ROS)-mediated mitochondrial pathway. In addition, RRP was found to dose-dependently induce autophagy, which occurred prior to apoptosis. RRP also primarily induced autophagy-mediated apoptosis in HCCCs via the PI3K/AKT/mTOR pathway. Thus, RRP might serve as a legitimate therapeutic drug candidates against human cervical cancer.

摘要

本研究旨在探讨刺梨多糖对人宫颈癌(HCCCs)的作用及其机制。从刺梨花瓣中分离得到一种新型刺梨多糖,命名为 RRp。RRp 由葡萄糖、半乳糖醛酸、甘露糖、鼠李糖、半乳糖、阿拉伯糖、木糖和葡萄糖醛酸组成(摩尔比:7.78:7.59:4.23:3.22:3.15:1.65:1.00),Mw 为 327.92 kDa。RRp 能显著抑制 HeLa 和 SiHa 细胞的增殖、迁移和细胞周期阻滞。此外,RRp 通过激活半胱氨酸天冬氨酸蛋白酶(caspase)家族蛋白和介导活性氧(ROS)介导的线粒体途径诱导细胞凋亡。此外,RRp 被发现能剂量依赖性地诱导自噬,自噬发生在凋亡之前。RRp 还通过 PI3K/AKT/mTOR 通路主要诱导 HCCCs 中的自噬介导的细胞凋亡。因此,RRp 可能成为治疗人宫颈癌的有效候选药物。

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