抗坏血酸依赖性和非抗坏血酸依赖性锰卟啉细胞毒性:锰卟啉基SOD模拟物通过抗坏血酸依赖性和非依赖性途径的抗癌活性。

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Report Pub Date : 2021-12-01 DOI:10.1080/13510002.2021.1917214
Bader Hasan, Artak Tovmasyan, Ines Batinic-Haberle, Ludmil Benov
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引用次数: 0

摘要

目的:本研究的目的是研究卟啉环外围修饰如何影响Mn卟啉(MnPs)基SOD模拟物的抗癌活性。方法:六种化合物:吡啶环上有短乙基链的MnTE-2-PyP;MnTnHexOE-2-PyP和mntnnoct -2- pyp具有线性的8原子烷基链,但前者在烷基链内有一个氧原子;研究了具有吡啶基和苯基取代基的MnTE-2-PyPhP和mntph -2- pyp。用pII和MDA-MB-231癌细胞系研究细胞毒性。采用MTT(3-[4,5-二甲基噻唑-2-基)]-2,5-二苯基溴化四唑)法测定细胞活力,采用硫代丹胺B法测定细胞增殖。结果:细胞摄取随着化合物亲脂性的增加而增加,而Mn(III)/Mn(II)氧化还原对的还原电位(E½)偏离了与抗坏血酸有效氧化还原循环的最佳值,这是ROS产生所必需的。然而,两亲性MnPs通过不涉及ROS的机制发挥抗癌活性。结论:两种不同的过程解释了MnPs的细胞毒性。具有适当E½的MnPs通过ros依赖机制起作用。具有合适结构的两亲性MnPs破坏敏感的细胞成分,导致增殖抑制和活力丧失。设计与敏感细胞靶点直接相互作用的化合物在开发具有高选择性和特异性的抗癌药物方面具有很大的前景。
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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Ascorbate-dependent and ascorbate-independent Mn porphyrin cytotoxicity: anticancer activity of Mn porphyrin-based SOD mimics through ascorbate-dependent and -independent routes.

Objective: The aim of this study was to investigate how modifications at the periphery of the porphyrin ring affect the anticancer activity of Mn porphyrins (MnPs)-based SOD mimics.

Methods: Six compounds: MnTE-2-PyP with a short ethyl chain on the pyridyl ring; MnTnHexOE-2-PyP and MnTnOct-2-PyP with linear 8-atom alkyl chains, but the former with an oxygen atom within the alkyl chain; MnTE-2-PyPhP and MnTPhE-2-PyP with pyridyl and phenyl substituents, were investigated. Cytotoxicity was studied using pII and MDA-MB-231 cancer cell lines. Viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide) assay and cell proliferation was determined by the sulforhodamine B assay.

Results: Cellular uptake was increased with the increase of the lipophilicity of the compounds, whereas reduction potential (E½) of the Mn(III)/Mn(II) redox couple shifted away from the optimal value for efficient redox cycling with ascorbate, necessary for ROS production. Amphiphilic MnPs, however, exerted anticancer activity by a mechanism not involving ROS.

Conclusion: Two different processes account for MnPs cytotoxicity. MnPs with appropriate E½ act via a ROS-dependent mechanism. Amphiphilic MnPs with suitable structure damage sensitive cellular constituents, leading to the suppression of proliferation and loss of viability. Design of compounds interacting directly with sensitive cellular targets is highly promising in the development of anticancer drugs with high selectivity and specificity.

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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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