Augmenting Chemotherapy Response in Ovarian Cancer: N-3 Polyunsaturated Fatty Acids Target TOP2A.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2025-06-02 DOI:10.2174/0109298673359261250504031207

Pradnya Gurav, Shubham Hajare, Venkateswara Swamy, Kedar R N

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引用次数: 0

Abstract

Introduction: Ovarian cancer, a significant contributor to global female mortality and the third most prevalent gynecological cancer in India, poses challenges for conventional treatments like chemotherapy and radiotherapy.

Method: This study explores the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the efficacy of chemotherapy, particularly doxorubicin (DOXO), in ovarian teratocarcinoma (PA-1) cells. Rigorous cell viability assays demonstrated that n-3 PUFAs in combination significantly enhanced DOXO-induced cytotoxicity, reducing cell survival and migration potential. N-3 PUFAs and DOXO synergistically reduced colony formation in the group receiving the combination treatment as seen in the clonogenic assays, as further validated by hanging drop and apoptosis assays results.

Results: Network pharmacological investigations pinpointed the gene topoisomerase II A (TOP2A) as a pivotal target, while molecular docking simulations revealed structural similarities between n-3 PUFAs (DHA or EPA) and DOXO, implying probable common mechanisms such as DNA intercalation and topoisomerase II inhibition. Molecular dynamics simulations delineated distinct interaction profiles for Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) with TOP2A, offering mechanistic insights. Combining computational and experimental methodologies reveals the synergistic benefits of n-3 PUFAs and DOXO in treating ovarian cancer, leading to improved therapeutic outcomes.

Conclusion: These results provide a comprehensive view of the potential of combining n-3 PUFAs with DOXO for more potent ovarian cancer treatments.

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卵巢癌化疗反应增强：N-3多不饱和脂肪酸靶向TOP2A

引言：卵巢癌是全球女性死亡的重要原因之一，也是印度第三大常见妇科癌症，对化疗和放疗等传统治疗提出了挑战。方法：本研究探讨了omega-3多不饱和脂肪酸（n-3 PUFAs）对化疗，特别是多柔比星（DOXO）对卵巢畸胎癌（PA-1）细胞疗效的影响。严格的细胞活力测定表明，n-3 PUFAs联合显著增强doxo诱导的细胞毒性，降低细胞存活和迁移潜力。N-3 PUFAs和DOXO在接受联合处理的组中协同减少了集落的形成，这在克隆生成实验中可以看到，并通过挂滴和凋亡实验结果进一步证实。结果：网络药理学研究确定了拓扑异构酶II A （TOP2A）基因是关键靶点，而分子对接模拟揭示了n-3 PUFAs （DHA或EPA）和DOXO之间的结构相似性，暗示可能存在DNA嵌入和拓扑异构酶II抑制等共同机制。分子动力学模拟描绘了二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）与TOP2A的不同相互作用谱，提供了机制上的见解。结合计算和实验方法揭示了n-3 PUFAs和DOXO在治疗卵巢癌中的协同作用，从而改善了治疗效果。结论：这些结果为n-3 PUFAs与DOXO联合治疗卵巢癌提供了一个全面的观点。

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

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.