Influence of pH on the cytotoxic activity of organic acids against breast cancer cells

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-07-22 DOI:10.1016/j.bmc.2025.118330

Sungmun Lee

{"title":"Influence of pH on the cytotoxic activity of organic acids against breast cancer cells","authors":"Sungmun Lee","doi":"10.1016/j.bmc.2025.118330","DOIUrl":null,"url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer among women worldwide. Unlike normal cells, breast cancer cells exhibit a reversed pH gradient characterized by a lower extracellular pH (pH<sub>e</sub>, ∼6.7–7.1) and a higher intracellular pH (pH<sub>i</sub>, ∼7.4). Modulation of extracellular pH can influence the growth and viability of these cells. In this study, we examined the effects of ten organic acids on MDA-MB-231 metastatic breast cancer cells. Among ten organic acids, dicarboxylic acids (succinic acid (SA), fumaric acid (FA), and tartaric acid (TA)) and tricarboxylic acid (citric acid (CA)) exhibited significantly higher cytotoxicity compared to the others including monocarboxylic acid. Further analysis revealed that their cytotoxic effects were primarily induced by acidic pH associated with the number of <img>COOH in their chemical structures. These acids also impacted cell viability, density, and morphology in both 2D cultures and 3D spheroid models. The results of this research can aid in the development of innovative anticancer drugs treating breast cancer.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118330"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089625002718","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Breast cancer is the most prevalent cancer among women worldwide. Unlike normal cells, breast cancer cells exhibit a reversed pH gradient characterized by a lower extracellular pH (pH_e, ∼6.7–7.1) and a higher intracellular pH (pH_i, ∼7.4). Modulation of extracellular pH can influence the growth and viability of these cells. In this study, we examined the effects of ten organic acids on MDA-MB-231 metastatic breast cancer cells. Among ten organic acids, dicarboxylic acids (succinic acid (SA), fumaric acid (FA), and tartaric acid (TA)) and tricarboxylic acid (citric acid (CA)) exhibited significantly higher cytotoxicity compared to the others including monocarboxylic acid. Further analysis revealed that their cytotoxic effects were primarily induced by acidic pH associated with the number of COOH in their chemical structures. These acids also impacted cell viability, density, and morphology in both 2D cultures and 3D spheroid models. The results of this research can aid in the development of innovative anticancer drugs treating breast cancer.

Abstract Image

查看原文本刊更多论文

pH值对有机酸对乳腺癌细胞毒活性的影响

乳腺癌是全世界女性中最常见的癌症。与正常细胞不同，乳腺癌细胞表现出相反的pH梯度，其特征是较低的细胞外pH （pHe, ~ 6.7-7.1）和较高的细胞内pH （pHi, ~ 7.4）。调节细胞外pH值可以影响这些细胞的生长和活力。在这项研究中，我们检测了十种有机酸对MDA-MB-231转移性乳腺癌细胞的影响。在10种有机酸中，二羧酸（琥珀酸（SA）、富马酸（FA）和酒石酸（TA））和三羧酸（柠檬酸（CA））的细胞毒性显著高于包括单羧酸在内的其他有机酸。进一步的分析表明，它们的细胞毒性作用主要是由与化学结构中COOH数量相关的酸性pH诱导的。在2D培养和3D球体模型中，这些酸也会影响细胞活力、密度和形态。这项研究的结果可以帮助开发治疗乳腺癌的创新抗癌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.