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Anti-Cancer Agents in Medicinal Chemistry

Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Investigation of Apoptotic and Anticancer Effects of 2-substituted Benzothiazoles in Breast Cancer Cell Lines: EGFR Modulation and Mechanistic Insights

Author(s): Muhammed Mehdi Uremis*, Mustafa Ceylan and Yusuf Turkoz

Volume 25, Issue 6, 2025

Published on: 29 October, 2024

Page: [433 - 445] Pages: 13

DOI: 10.2174/0118715206335840241018053929

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Abstract

Background and Objective: Benzothiazole derivatives, a class of heterocyclic compounds, exhibited diverse biological activities influenced by substituents in the thiazole ring. This study aimed to synthesize these compounds with two functional groups to investigate their potential as anticancer agents, particularly against breast cancer. While previous research demonstrated the efficacy of 2-substituted benzothiazoles against glioma and cervical and pancreatic cancer cells, there is a gap in studies targeting breast cancer.

Methods: The synthesized compounds were tested in vitro using MCF-7, MDA-MB-231, and MCF-10A cell lines, with Doxorubicin as the positive control. Various assays were conducted, including Annexin V/PI, cell cycle analysis, wound healing, and measurement of mitochondrial membrane potential. Protein expression of EGFR and transcription levels of apoptosis-related genes (Bax and Bcl-xL) and cancer progression-related genes (JAK, STAT3, ERK, AKT, mTOR) were analyzed. Additionally, the balance between antioxidants and oxidants was evaluated by measuring TAS and TOS levels.

Results: Our findings revealed that benzothiazole compounds significantly inhibited breast cancer cell growth by reducing cell motility, disrupting mitochondrial membrane potential, and inducing cell cycle arrest in the sub-G1 phase. These compounds increased reactive oxygen species accumulation, leading to cell death. Furthermore, they decreased EGFR protein levels, increased Bax gene transcription, and downregulated the expression of genes such as JAK, STAT3, ERK, AKT, and mTOR.

Conclusion: In conclusion, benzothiazole derivatives exhibited potent inhibitory effects on breast cancer in vitro by promoting apoptosis, downregulating EGFR activity, and modulating key signaling pathways, including JAK/STAT, ERK/MAPK, and PI3K/Akt/mTOR. These results highlighted the potential of benzothiazole derivatives as novel therapeutic agents for breast cancer treatment.

Keywords: Benzothiazole, EGFR, JAK/STAT, MAPK/ERK, PI3K/AKT/mTOR, MCF-7, MDA-MB-231.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

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