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胡椒碱介导的子宫颈癌细胞凋亡超出对接预测。

Piperlongumine mediated apoptosis in cervical cancer cells beyond docking predictions.

作者信息

Parveen Shama, Ahtsham Ana, Kumar Saurabh, Gupta Pratishtha, Ghous Faraz, Banerjee Monisha

机构信息

Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh 226007, India.

Department of Chemistry, University of Lucknow, Lucknow, Uttar Pradesh 226007, India.

出版信息

Toxicol Rep. 2025 Apr 23;14:102031. doi: 10.1016/j.toxrep.2025.102031. eCollection 2025 Jun.

Abstract

Cervical cancer is the 4th most prevalent cancer in women. Despite its global health impact, cervical cancer research has achieved limited success with various therapies (chemo, radio, chemo-radio, surgery, etc.). Recent decades have seen no improvement in survival rates due to cancer recurrence and long-term health concerns. These treatments show the need for a new herbal approach as alternative therapy for cancer. Piperlongumine is one of numerous perfected phytochemicals with anticancerous properties. In this study, in silico simulations demonstrate various novel properties of Piperlongumine. Molecular docking was performed between receptor and ligand by simulating molecular interactions in the pro and anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Bcl-2 antagonist/killer (Bak). The docking scores of Piperlongumine with Bcl-2, Bak, and Bax are -7.02, -6.78, and -7.54 kcal/mol, respectively. Piperlongumine was also bio-tested for anticancer activities against cervical cancer cells (SiHa). Piperlongumine showed compromised cell viability, promoted apoptosis, higher nuclear condensation, reduction in mitochondrial membrane potential, increase in reactive oxygen species level, promoted cell cycle arrest, upregulation of pro-apoptotic gene whereas downregulation of anti-apoptotic genes. studies revealed that Piperlongumine targets apoptotic pathway in cervical cancer and could be a possible effective treatment for cervical cancer. Additional research is needed to explore the potential of Piperlongumine to improve treatment outcomes.

摘要

宫颈癌是女性中第四大常见癌症。尽管其对全球健康有影响,但宫颈癌研究在各种治疗方法(化疗、放疗、放化疗、手术等)方面取得的成功有限。近几十年来,由于癌症复发和长期健康问题,生存率没有提高。这些治疗方法表明需要一种新的草药方法作为癌症的替代疗法。荜茇酰胺是众多具有抗癌特性的精制植物化学物质之一。在这项研究中,计算机模拟展示了荜茇酰胺的各种新特性。通过模拟促凋亡和抗凋亡蛋白B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)和Bcl-2拮抗剂/杀手(Bak)中的分子相互作用,进行了受体与配体之间的分子对接。荜茇酰胺与Bcl-2、Bak和Bax的对接分数分别为-7.02、-6.78和-7.54千卡/摩尔。还对荜茇酰胺针对宫颈癌细胞(SiHa)的抗癌活性进行了生物测试。荜茇酰胺显示细胞活力受损、促进细胞凋亡、核浓缩增加、线粒体膜电位降低、活性氧水平升高、促进细胞周期停滞、促凋亡基因上调而抗凋亡基因下调。研究表明,荜茇酰胺靶向宫颈癌的凋亡途径,可能是宫颈癌的一种有效治疗方法。需要进一步的研究来探索荜茇酰胺改善治疗效果的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be9/12063131/4d7b7beb78fe/gr1.jpg

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