Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea.
Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;
Anticancer Res. 2024 Oct;44(10):4301-4307. doi: 10.21873/anticanres.17259.
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.
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.
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.
Valrubicin, through drug repositioning, can be applied as a new therapeutic agent for OC.
背景/目的：卵巢癌（OC）是导致女性癌症相关死亡的主要原因，因此仍迫切需要新的治疗药物来改善患者的预后。本研究旨在通过筛选食品和药物管理局 (FDA) 批准的化合物库来探索药物重定位，以确定对 OC 具有治疗潜力的化合物。我们还旨在阐明这些化合物的作用机制，以更好地了解它们如何抑制癌细胞增殖。
使用 WST-1 测定法，筛选了 1710 种 FDA 批准的药物库，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) 测定和免疫印迹分析评估选定化合物作用的分子机制。
筛选 FDA 批准的文库显示，盐酸表柔比星是 OVCAR8 细胞增殖和 SKOV3 和 A2780 细胞生长的有效抑制剂。此外，盐酸表柔比星处理导致 DNA 片段化增加，TUNEL 测定证实了这一点，并通过增强裂解的 caspase-3 和多聚（ADP-核糖）聚合酶水平激活凋亡信号。
盐酸表柔比星通过药物重定位可作为 OC 的一种新的治疗药物。
