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新型水溶性甲基咪唑基氧化钒(IV)配合物对三阴性乳腺癌的多方面抗肿瘤疗效

Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex against triple negative mammary carcinoma.

作者信息

Ghosh Noyel, De Samhita, Pramanik Nikhil Ranjan, Sil Parames C

机构信息

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.

Department of Chemistry, Bidhannagar College, EB-2, Salt Lake, Kolkata 700064, India.

出版信息

Cell Signal. 2024 May;117:111089. doi: 10.1016/j.cellsig.2024.111089. Epub 2024 Feb 7.

Abstract

A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non‑platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo. OVMI has been reported to generate cytotoxicity in human triple negative breast carcinoma cells, MDA-MB-231 as well as in mouse 4T1 cells by priming them for apoptosis. ROS-mediated, mitochondria-dependent as well as ER-stress-evoked apoptotic death seemed to be main operational hub guiding the cytotoxicity of OVMI in vitro. Moreover, OVMI has been noticed to elicit antimetastatic effect in vitro. Therapeutic application of OVMI has been extended on 4T1-based mammary tumor of female Balb/c mice, where it has been found to reduce tumor size, volume and restore general tissue architecture successfully to a great extent. Apart from that, OVMI has been documented to limit 4T1-based secondary pulmonary metastasis along with being non-toxic and biocompatible in vivo.

摘要

据报道,一系列以钒为金属中心的配合物具有广泛的抗肿瘤特性,属于非铂金属药物系列,并且从铂类药物的作用机制来看,有望提供替代治疗策略。尽管钒配合物对多种动物和移植性人类癌症的抗肿瘤活性已有文献记载,但其确切的作用机制仍有待揭示。在本研究中,一种新型的水溶性1-甲基咪唑取代的基于二吡啶甲酸的氧化钒(IV)配合物(OVMI)已在体外和体内对乳腺癌的抗肿瘤特性进行了评估。据报道,OVMI通过引发人三阴性乳腺癌细胞MDA-MB-231以及小鼠4T1细胞凋亡而产生细胞毒性。ROS介导的、线粒体依赖性以及内质网应激诱发的凋亡死亡似乎是指导OVMI体外细胞毒性的主要作用枢纽。此外,已注意到OVMI在体外具有抗转移作用。OVMI的治疗应用已扩展到雌性Balb/c小鼠基于4T1的乳腺肿瘤,在那里发现它能成功地在很大程度上减小肿瘤大小、体积并恢复一般组织结构。除此之外,已证明OVMI能限制基于4T1的继发性肺转移,并且在体内无毒且具有生物相容性。

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