In Vitro Study on the Antitumor Bioactivity of Anderson-Type Polyoxometalates.

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current pharmaceutical design Pub Date : 2025-04-22 DOI:10.2174/0113816128367617250323075703

Chenguang Yao, Ting Tan, Jiangning Yan, Zijia Zhao, Romina Onintsoa Diarimalala, Junjie Wang, William Wang, Hanluo Li, Jingbiao Liu, Yanhong Wei, Kanghong Hu

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引用次数: 0

Abstract

Objective: To develop new Anderson-type polyoxometalates (POMs) with high efficiency and low cytotoxicity, and investigate the effects and mechanisms against lung (A549), cervical (Hela), and breast cancer (MCF7) cell lines.

Methods: Cytotoxicity assessments on Hela, A549, and MCF-7 tumor cells were tested by MTT assay. Antitumor activities of B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxylmodified) were detected by apoptosis, scratch, and colony formation assay. The antitumor molecular mechanisms were explored by western blotting.

Results: This study synthesized and evaluated twelve Anderson-type compounds which were centered with vanadium, chromium, iron, cobalt, nickel, and copper heteroatoms, modified with methyl and hydroxyl at the side chains. Cytotoxicity assessments revealed that compounds B1 and B7 exhibited superior efficacy, with IC50 values of approximately 7 μmol/L of three cell lines. B1 and B7 inhibited proliferation and migration in these cell lines and induced apoptosis in MCF7 and A549 cells. Mechanistic investigations indicated that B1 induces apoptosis in MCF7 cells by inhibiting the AKT signaling pathway and downregulating the expression of apoptosis-related proteins Bcl-2 and Caspase-9.

Conclusion: Novel Anderson-type POMs B1 (vanadium-centered, methyl-modified) and B7 (vanadiumcentered, hydroxyl-modified) exhibited superior efficacy against tumor cells and induced apoptosis via PI3K/ AKT pathway, which provides new theoretical avenues for developing POM-mediated antitumor chemotherapeutic medications.

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安德森型多金属氧酸酯抗肿瘤生物活性的体外研究。

目的：开发高效、低细胞毒性的新型anderson型多金属氧酸盐（pom），探讨其对肺癌（A549）、宫颈癌（Hela）和乳腺癌（MCF7）细胞系的作用及其机制。方法：采用MTT法检测Hela、A549、MCF-7肿瘤细胞的细胞毒性。通过细胞凋亡、划痕和集落形成实验检测B1（钒中心，甲基修饰）和B7（钒中心，羟基修饰）的抗肿瘤活性。western blotting分析其抗肿瘤分子机制。结果：本研究合成并评价了12个以钒、铬、铁、钴、镍和铜为中心杂原子，在侧链上进行甲基和羟基修饰的anderson型化合物。细胞毒性评价表明，化合物B1和B7对三种细胞系的IC50值均在7 μmol/L左右，具有较好的抑制作用。B1和B7抑制MCF7和A549细胞的增殖和迁移，诱导细胞凋亡。机制研究表明，B1通过抑制AKT信号通路，下调凋亡相关蛋白Bcl-2和Caspase-9的表达，诱导MCF7细胞凋亡。结论：新型anderson型POMs B1（以钒为中心，甲基修饰）和B7（以钒为中心，羟基修饰）对肿瘤细胞具有较好的杀伤作用，并通过PI3K/ AKT通路诱导细胞凋亡，为开发POMs介导的抗肿瘤化疗药物提供了新的理论途径。

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 pharmaceutical design 医学-药学

CiteScore

6.30

自引率

0.00%

发文量

302

审稿时长

2 months

期刊介绍： Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field. Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.