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

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dc.contributor.authorUremis, Muhammed Mehdi
dc.contributor.authorCeylan, Mustafa
dc.contributor.authorTurkoz, Yusuf
dc.date.accessioned2026-04-04T13:32:56Z
dc.date.available2026-04-04T13:32:56Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground 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.
dc.identifier.doi10.2174/0118715206335840241018053929
dc.identifier.endpage445
dc.identifier.issn1871-5206
dc.identifier.issn1875-5992
dc.identifier.issue6
dc.identifier.pmid39473208
dc.identifier.scopus2-s2.0-105001319235
dc.identifier.scopusqualityQ2
dc.identifier.startpage433
dc.identifier.urihttps://doi.org/10.2174/0118715206335840241018053929
dc.identifier.urihttps://hdl.handle.net/11616/108802
dc.identifier.volume25
dc.identifier.wosWOS:001346831100001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectBenzothiazole
dc.subjectEGFR
dc.subjectJAK/STAT
dc.subjectMAPK/ERK
dc.subjectPI3K/AKT/mTOR
dc.subjectMCF-7
dc.subjectMDA-MB-231
dc.titleInvestigation of Apoptotic and Anticancer Effects of 2-substituted Benzothiazoles in Breast Cancer Cell Lines: EGFR Modulation and Mechanistic Insights
dc.typeArticle

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