Thiosemicarbazide Derivative of Captopril (8) imposes Cellular-Dependent Death Modalities on Breast Cancer Cell Lines.

Q2 Medicine

Asian Pacific Journal of Cancer Prevention Pub Date : 2025-06-01 DOI:10.31557/APJCP.2025.26.6.2061

Baan M Al-Jasani, Hayder B Sahib, Hiba N Al-Saad

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引用次数: 0

Abstract

Objective: Breast cancer prevalence is continuing to rise worldwide. Despite the diversity of the current approaches and protocols to treat this heterogeneous disease, most of these face the challenges of side effects and resistance. Hence, novel and innovative approaches to the treatment of breast cancer are almost constantly needed. This study aimed to investigate the antiproliferative and death modalities induced by three thiosemicarbazide derivatives of captopril in two subtypes of breast cancer cell lines, the Estrogen- receptor positive MCF-7, and the Estrogen/progesterone- receptor-negative AMJ13.

Methods: MTT assay was used to determine the cytotoxicity of the derivatives and their parent compound Captopril, Hematoxylin and Eosin (H&E) staining, Acridine Orange/ Ethidium Bromide (AO/EtBr) staining, Caspase immunocytochemistry analysis and ROS generation by Human ROMO1 ELISA assays were conducted to explore the type of cellular death induced by these derivatives.

Results: One of the derivatives denoted as (8) demonstrated the best antiproliferative profile recording the highest cytotoxic effect with IC50 of (88.06 µM) and (66.82 µM) compared to that of captopril (849.8 µM),(1075µM) in MCF-7 and AMJ13 breast cancer cells respectively. In MCF-7 cells, derivative (8) imposed an apoptotic cellular death with the involvement of caspase-3, and caspase-9 and displayed a time-dependent ROS generation. In AMJ13 breast cancer cells, results revealed an extensive vacuole forming, non-apoptotic cellular death, without ROS generation, but with a significant implication of caspase-9. Conclusion: This study demonstrated the thiosemicarbazide derivative of captopril (8) as a promising antiproliferative agent against breast cancer cells displaying different cellular death modalities, signifying the versatility of the derivative and suggesting multitarget pathways. This study strongly recommends derivative (8) as a future leading molecule.

查看原文本刊更多论文

卡托普利的硫代氨基脲衍生物(8)对乳腺癌细胞系施加细胞依赖性死亡模式。

目的：乳腺癌患病率在世界范围内持续上升。尽管目前治疗这种异质性疾病的方法和方案多种多样，但其中大多数都面临副作用和耐药性的挑战。因此，不断需要新的和创新的方法来治疗乳腺癌。本研究旨在探讨卡托普利的三种硫代氨基脲衍生物对雌激素受体阳性的MCF-7和雌激素/孕激素受体阴性的AMJ13两种乳腺癌细胞系的抗增殖和死亡模式。方法：采用MTT法测定其衍生物及其母体化合物卡托普、苏木精和伊红（H&E）染色、吖啶橙/溴化乙啶（AO/EtBr）染色、Caspase免疫细胞化学分析和人ROMO1酶联免疫吸附试验（ELISA）测定ROS生成情况，探讨其诱导细胞死亡的类型。结果：与卡托普利（849.8µM）、（1075µM）相比，其中一种衍生物(8)在MCF-7和AMJ13乳腺癌细胞中表现出最好的抗增殖作用，IC50分别为（88.06µM）和（66.82µM）。在MCF-7细胞中，衍生物(8)在caspase-3和caspase-9的参与下导致细胞凋亡，并显示出时间依赖性的ROS生成。在AMJ13乳腺癌细胞中，结果显示广泛的液泡形成，非凋亡细胞死亡，不产生ROS，但与caspase-9有显著关系。结论：本研究表明卡托普利的硫代氨基脲衍生物(8)是一种很有前景的抗乳腺癌细胞增殖药物，显示出不同的细胞死亡模式，这表明该衍生物的多功能性和多靶点途径。本研究强烈推荐衍生物(8)作为未来的先导分子。

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

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

CiteScore

2.80

自引率

0.00%

发文量

779

审稿时长

3 months

期刊介绍： Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: -Epidemiology, detection and screening. -Cellular research and bio-markers. -Identification of bio-targets and agents with novel mechanisms of action. -Optimal clinical use of existing anti-cancer agents, including combination therapies. -Radiation and surgery. -Palliative care. -Patient adherence, quality of life, satisfaction. -Health economic evaluations.