Selenium Nanoparticles Show Anticancer Activity Through Regulation of HIF-1α and HIF-2α Under Hypoxic Condition in Liver Cancer Cells.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sancharan Acharya, Subramaniyam Nithyananthan, Chinnasamy Thirunavukkarasu
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引用次数: 0

Abstract

Tumor microenvironment has significant influence in therapeutic response and clinical outcome. Combination therapy is more effective in cancer treatment compared with monotherapy. Any chemical or drug that targets tumor microenvironment pathway, will be a boon to combination cancer chemotherapy. Combination therapy through micronutrient may have added advantage in clinical applications. Selenium (Se) is an essential micronutrient; Se in the form of Se nanoparticles (SeNPs) show efficient anticancer properties and may have the potential to target tumor niche such as hypoxic environment. The aim of this study was to find out the anticancer effect of SeNPs on cell line HepG2 under hypoxic condition and also to evaluate their effect on the translocation of hypoxia-inducible factors (HIFs) from cytoplasm to nucleus that help the cells to survive under hypoxic condition. It was found that the SeNPs induce HepG2 cell death in normoxic and hypoxic conditions, however, hypoxic condition showed higher LD50. SeNP concentration is directly proportional to cell death in both the conditions. Furthermore, intracellular accumulation of Se is not affected by hypoxia. SeNP-induced HepG2 cell death is due to increased DNA damage, nuclear condensation, and mitochondrial membrane potential disturbance. Furthermore, SeNPs were also found to decrease the translocation of HIFs from cytosol to the nucleus. After analyzing the results, it is concluded that SeNP treatment disturbs tumor niche through the inhibition of HIFs' translocation from cytosol to nucleus. SeNPs in synergy with primary drug, such as doxorubicin (DOX), may enhance the anticancer efficacy of DOX through regulation of HIFs, warranting further research.

低氧条件下,硒纳米颗粒通过调控肝癌细胞HIF-1α和HIF-2α显示抗癌活性。
肿瘤微环境对治疗反应和临床转归有重要影响。联合治疗比单药治疗更有效。任何靶向肿瘤微环境通路的化学物质或药物,都将是癌症联合化疗的福音。微量营养素联合治疗可能在临床应用中具有额外的优势。硒(Se)是人体必需的微量营养素;硒以硒纳米粒子(SeNPs)的形式表现出有效的抗癌特性,可能具有靶向肿瘤生态位(如缺氧环境)的潜力。本研究旨在探讨SeNPs在缺氧条件下对HepG2细胞株的抗癌作用,并评价其对缺氧诱导因子(hif)从细胞质向细胞核转运的影响,从而帮助细胞在缺氧条件下存活。结果发现,在常氧和缺氧条件下,SeNPs均可诱导HepG2细胞死亡,但缺氧条件下LD50较高。在两种情况下,SeNP浓度与细胞死亡成正比。此外,细胞内硒的积累不受缺氧的影响。senp诱导的HepG2细胞死亡是由于DNA损伤增加、核凝聚和线粒体膜电位紊乱。此外,还发现SeNPs减少了hif从细胞质到细胞核的易位。分析结果表明,SeNP治疗通过抑制hif从细胞质向细胞核的易位来扰乱肿瘤生态位。SeNPs与主要药物如阿霉素(DOX)协同作用,可能通过调节hfs增强DOX的抗癌功效,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
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