Repurposing Valrubicin as a Potent Inhibitor of Ovarian Cancer Cell Growth.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-10-01 DOI:10.21873/anticanres.17259

Jaeeun Lee, Kyun Heo

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引用次数: 0

Abstract

Background/aim: Ovarian cancer (OC) is a leading cause of cancer-related mortality among women, and there remains a significant unmet need for new therapeutic agents to improve patient outcomes. This study aimed to explore drug repositioning by screening a library of Food and Drug Administration (FDA)-approved compounds to identify those with therapeutic potential against OC. We also aimed to elucidate the molecular mechanisms of action of such compounds to better understand how they inhibit cancer cell proliferation.

Materials and methods: Using the WST-1 assay, a library of 1710 FDA-approved drugs was screened to evaluate their effects on OC cell proliferation. The molecular mechanisms underlying the effects of selected compounds were assessed through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunoblot analysis.

Results: Screening of FDA-approved libraries revealed valrubicin as a potent inhibitor of OVCAR8 cell proliferation and SKOV3 and A2780 cell growth. Furthermore, valrubicin treatment led to increased DNA fragmentation, as evidenced by the TUNEL assay, and activated apoptosis signaling through enhancement of cleaved caspase-3 and poly(ADP-ribose) polymerase levels.

Conclusion: Valrubicin, through drug repositioning, can be applied as a new therapeutic agent for OC.

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重塑 Valrubicin 作为卵巢癌细胞生长强效抑制剂的用途。

背景/目的：卵巢癌（OC）是导致女性癌症相关死亡的主要原因之一，目前仍有大量新的治疗药物需求未得到满足，无法改善患者的预后。本研究旨在通过筛选食品药品管理局（FDA）批准的化合物库来探索药物的重新定位，以确定那些对卵巢癌具有治疗潜力的化合物。我们还旨在阐明这些化合物的分子作用机制，以便更好地了解它们是如何抑制癌细胞增殖的：使用 WST-1 试验筛选了 1710 种经 FDA 批准的药物，以评估它们对 OC 细胞增殖的影响。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）检测和免疫印迹分析评估了所选化合物作用的分子机制：结果：对美国 FDA 批准的化合物库进行筛选后发现，valrubicin 是 OVCAR8 细胞增殖以及 SKOV3 和 A2780 细胞生长的强效抑制剂。此外，valrubicin 处理会导致 DNA 断裂增加（TUNEL 检测证明了这一点），并通过提高裂解的 caspase-3 和聚（ADP-核糖）聚合酶水平激活细胞凋亡信号：结论：通过药物重新定位，缬氨嘧啶可作为一种新的治疗 OC 的药物。

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

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.