Coskun K. A., Abay E. C., Gümüş M., Çelik A. B., Gulum L., Koca İ., ...More
BIOLOGY, vol.14, no.9, pp.1193-1218, 2025 (SCI-Expanded, Scopus)
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Publication Type:
Article / Article
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Volume:
14
Issue:
9
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Publication Date:
2025
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Doi Number:
10.3390/biology14091193
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Journal Name:
BIOLOGY
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Journal Indexes:
Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Veterinary Science Database, Directory of Open Access Journals
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Page Numbers:
pp.1193-1218
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Open Archive Collection:
AVESIS Open Access Collection
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Yozgat Bozok University Affiliated:
Yes
Abstract
Background: Breast cancer is the most common cancer among women. Although doxorubicin (DOX) is widely used in its treatment, its dose-dependent toxicity and the development of drug resistance reduce its therapeutic efficacy. Therefore, this study aims to identify a novel anticancer agent that is more effective than DOX, inhibits cancer cell growth, and is less toxic to healthy cells. Methods: The cytotoxic effects of DOX and 2S-series molecules were evaluated on human (MDA-MB-231) and mouse (4T1) TNBC breast cancer cell lines and healthy breast epithelial (hTERT) cells using MTT assays at 48 and 72 h to screen functional similarities and possible differences upon drug/inhibitor treatment. Apoptosis and cell cycle analysis were analyzed by flow cytometry. Gene expression profiles were assessed by qPCR, and binding interactions with Hsp90 were examined via molecular docking. Results: 2S-5 exhibited IC50 values of 6.21 µM (MDA-MB-231) and 7.04 µM (4T1), while 2S-13 showed IC50 values of 7.73 µM and 8.21 µM, respectively. Both compounds demonstrated selective cytotoxicity against cancer cells. Gene expression and pathway analysis revealed that 2S-13 modulated the PI3K-Akt, MAPK, apoptosis, and HIF-1 pathways, showing broader modulation than DOX. Conclusions: 2S-13 appears to be a promising drug candidate, particularly in the MDA-MB-231 cell line. However, the current findings are limited to in vitro models. Further in vivo studies and pharmacokinetic analyses are required to validate its therapeutic potential, assess long-term efficacy and safety, and explore its resistance profile and molecular mechanisms in more detail.