香叶醇通过HIF-1α/BNIP3/Beclin-1信号通路诱导A549 CoCl2处理细胞发生自噬/凋亡

Autophagy/ Apoptosis Induced by Geraniol through HIF-1α/BNIP3/Beclin-1 Signaling Pathway in A549 CoCl2 Treated Cells.

作者信息

Abo El-Ella Dina M

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, 6 October City, 12566, Giza, Egypt.

出版信息

Adv Pharm Bull. 2022 Jan;12(1):155-162. doi: 10.34172/apb.2022.016. Epub 2020 Oct 18.

Abstract

During cancer growth, hypoxia occurs along with autophagy as an adaptive responseto overcome cellular stress. Geraniol (GE) is a natural isoprenoid known for its wide anticanceractivity and autophagy induction in the cancer cell. To investigate the antihypoxic potential ofGE with the incidence of autophagy and apoptotic cell death in A549 CoCl treated cells. A549 cells were incubated for 24 hours with GE and CoCl either alone or incombination. We examined the cytotoxicity and cell viability of GE either alone or incombination therapy using MTT and trypan blue assay.GE modulating effect was determined onlipid peroxidation, antioxidant capacity markers, gene expression levels of hypoxia induciblefactor-1 (HIF-1), NF-κB, vascular endothelial growth factor (VEGF), autophagy factors in differentgroups, besides apoptotic bodies using acridine orange/ethidium bromide (AO/EB). GE and CoCl combination therapy downregulated the expression of HIF-1α thatsuppressed A549 cell growth through downregulation of BNIP3 and beclin-1 gene expression.This resulted in autophagy and apoptotic cell death, in addition to the downregulation of NF-kBand VEGF expression. Also, GE treatment significantly reduced the oxidative stress markers andrestored the antioxidant capacity. GE possesses an antihypoxic effect on A549 CoCl treated cells and induces celldeath via autophagy along with apoptosis through HIF-1α/BNIP3/beclin-1 signaling pathway.

摘要

在癌症生长过程中,缺氧与自噬同时出现,作为一种适应性反应以克服细胞应激。香叶醇(GE)是一种天然类异戊二烯,以其广泛的抗癌活性和在癌细胞中诱导自噬而闻名。为了研究GE对A549细胞经氯化钴(CoCl)处理后自噬发生率和凋亡细胞死亡的抗缺氧潜力。将A549细胞单独或联合用GE和CoCl孵育24小时。我们使用MTT和台盼蓝试验检测了GE单独或联合治疗的细胞毒性和细胞活力。除了使用吖啶橙/溴化乙锭(AO/EB)检测凋亡小体外,还测定了GE对不同组中脂质过氧化、抗氧化能力标志物、缺氧诱导因子-1(HIF-1)、核因子-κB(NF-κB)、血管内皮生长因子(VEGF)、自噬因子基因表达水平的调节作用。GE和CoCl联合治疗下调了HIF-1α的表达,通过下调BNIP3和beclin-1基因表达抑制了A549细胞生长。这除了下调NF-κB和VEGF表达外,还导致了自噬和凋亡细胞死亡。此外,GE处理显著降低了氧化应激标志物并恢复了抗氧化能力。GE对A549 CoCl处理的细胞具有抗缺氧作用,并通过HIF-1α/BNIP3/beclin-1信号通路诱导细胞通过自噬和凋亡死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8a0/9012915/271a72a80774/apb-12-155-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索