Khalifa Ashraf, Balthazar Joseph D, Subash-Babu Pandurangan, Zaky Mohamed Y, El-Moaty Zeinab A, M Ibrahim Hairul Islam
Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia.
Division of Microbiology and Biotechnology, Entomology Research Institute, Loyola College, Chennai 600034, Tamil Nadu, India.
Pharmaceuticals (Basel). 2025 Apr 24;18(5):620. doi: 10.3390/ph18050620.
Actinomycetes, particularly species within the genus, are renowned for their ability to produce a wide array of bioactive molecules with therapeutic potential. This study aimed to comprehensively investigate the antimicrobial and anticancer properties of ERI-15, with a particular focus on a purified compound, 2-amino-3-chlorobenzoic acid (2A3CB), and its efficacy against microbial pathogens and breast cancer cell lines. Antimicrobial compounds were produced through fermentation techniques and isolated via column chromatography. Bioassay-guided fractionation was conducted against (ATCC 25923), methicillin-resistant (MRSA), (ATCC 25922), and (ATCC 441). Major fractions were further purified using preparative thin-layer chromatography (TLC). The structures of active compounds were elucidated using spectral analyses including IR, mass spectrometry, and H/C NMR. The compound 2A3CB (/ 171) was tested against MDA-MB-231 and 3T3 cell lines. Cytotoxicity was assessed by the MTT assay, and apoptotic mechanisms were explored via cell proliferation assays, dual fluorescent staining, migration and invasion assays, and analysis of apoptotic markers at mRNA and protein levels. 2A3CB exhibited strong cytotoxic effects on MDA-MB-231 cells, with IC values of 26 µM, 5 µM, and 7.2 µM at 24, 48, and 72 h, respectively. It significantly inhibited cell proliferation and migration, and induced apoptosis via caspase-mediated pathways. Expression levels of PTEN, PCNA, BAX, and STAT3 were downregulated, suggesting inhibition of metastasis through the suppression of invasion and migration. The results demonstrate that 2A3CB, derived from ERI-15, possesses potent antimicrobial and anticancer properties. Its ability to inhibit growth and induce apoptosis in MDA-MB-231 breast cancer cells highlights its potential as a natural therapeutic candidate for targeted cancer treatment, particularly in breast cancer progression.
放线菌，尤其是该属内的物种，以其产生大量具有治疗潜力的生物活性分子的能力而闻名。本研究旨在全面调查ERI - 15的抗菌和抗癌特性，特别关注一种纯化化合物2 - 氨基 - 3 - 氯苯甲酸（2A3CB）及其对微生物病原体和乳腺癌细胞系的功效。抗菌化合物通过发酵技术产生，并通过柱色谱法分离。针对金黄色葡萄球菌（ATCC 25923）、耐甲氧西林金黄色葡萄球菌（MRSA）、大肠杆菌（ATCC 25922）和铜绿假单胞菌（ATCC 441）进行生物测定指导的分级分离。主要级分使用制备型薄层色谱（TLC）进一步纯化。使用包括红外光谱、质谱和氢碳核磁共振在内的光谱分析来阐明活性化合物的结构。化合物2A3CB（/ 171）针对MDA - MB - 231和3T3细胞系进行测试。通过MTT法评估细胞毒性，并通过细胞增殖测定、双荧光染色、迁移和侵袭测定以及在mRNA和蛋白质水平分析凋亡标志物来探索凋亡机制。2A3CB对MDA - MB - 231细胞表现出强烈的细胞毒性作用，在24、48和72小时时的IC值分别为26 μM、5 μM和7.2 μM。它显著抑制细胞增殖和迁移，并通过半胱天冬酶介导的途径诱导凋亡。PTEN、PCNA、BAX和STAT3的表达水平下调，表明通过抑制侵袭和迁移来抑制转移。结果表明，源自ERI - 15的2A3CB具有强大的抗菌和抗癌特性。其抑制MDA - MB - 231乳腺癌细胞生长并诱导凋亡的能力突出了其作为靶向癌症治疗，特别是在乳腺癌进展中的天然治疗候选物的潜力。
