Diosmin induces mitochondrial-mediated apoptosis and anti-inflammatory effects in Hep-2 cells: an integrated in vitro and in silico analysis.

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Muthusamy Rajasekar, Kathiresan Suresh, Azhamuthu Theerthu, Ravichandran Pugazhendhi, Kathiresan Sivakumar
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Abstract

The present study aims to explore the anticancer efficacy of Diosmin by inducing mitochondrial-mediated apoptosis in human epidermoid carcinoma cells (Hep-2). This is done by cell line assays and studying crucial inflammatory and apoptotic signaling molecules. The cytotoxicity property of Diosmin was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Marker expression study was done by western blotting for studying apoptotic markers like Bax, Bcl-2, p53, Bak, and Bcl-xl, proinflammatory cytokine (TNF-α), interleukins (IL-1, IL-6, IL-8), and signal transduction (STAT-3). The docking study confirms the affinity of Diosmin with apoptotic and important markers. Through the MTT assay, a dose-dependent cytotoxic effect of Diosmin was unveiled, with an IC50 value of effective inhibition of cell proliferation. Diosmin treatment resulted in noteworthy downregulation of Bcl-xl, Bak, Bcl-2, IL-1, 6, 8, TNF-α, and STAT-3 while upregulating the p53 and Bax expression levels, highlighting its inhibitory role in inducing apoptosis. Docking studies further exposed robust binding affinities between Diosmin and target apoptotic proteins, suggesting its efficacy in disrupting cellular functions and inflammatory signaling pathways in Hep-2 cells. The cytotoxic effects on Hep-2 cells and suggested activation of Bax, p53, and inhibition of Bcl-xl, Bak, Bcl-2, IL-1, 6, 8, TNF-α, as well as STAT-3 lead to the activation of mitochondrial-mediated apoptosis in Diosmin-treated Hep-2 cells. Further, its anti-inflammatory properties locate Diosmin as a conclusive compound for further studies for effective oral and other related squamous carcinoma treatments.

地奥司明诱导Hep-2细胞线粒体介导的细胞凋亡和抗炎作用:体外和体内综合分析。
本研究旨在探讨薯蓣皂苷通过诱导线粒体介导的人表皮样癌细胞(Hep-2)凋亡的抗癌作用。这是通过细胞系分析和研究关键的炎症和凋亡信号分子来完成的。采用MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑)测定法评价了地奥米明的细胞毒性。细胞凋亡标志物Bax、Bcl-2、p53、Bak、Bcl-xl、促炎细胞因子(TNF-α)、白细胞介素(IL-1、IL-6、IL-8)、信号转导(STAT-3)表达研究。对接研究证实了Diosmin与凋亡和重要标志物的亲和力。通过MTT实验,揭示了地奥司明的剂量依赖性细胞毒作用,其IC50值有效抑制细胞增殖。地奥司明可下调Bcl-xl、Bak、Bcl-2、IL-1、6、8、TNF-α、STAT-3,上调p53和Bax表达水平,显示其在诱导细胞凋亡中的抑制作用。对接研究进一步揭示了Diosmin与靶凋亡蛋白之间强大的结合亲和性,提示其在破坏Hep-2细胞的细胞功能和炎症信号通路方面的功效。在diosmin处理的Hep-2细胞中,对Hep-2细胞的细胞毒性作用以及Bax、p53的激活,以及Bcl-xl、Bak、Bcl-2、IL-1、6、8、TNF-α和STAT-3的抑制导致线粒体介导的凋亡活化。此外,其抗炎特性使地奥司明成为进一步研究有效口服和其他相关鳞癌治疗的结论性化合物。
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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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