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Investigation of cytotoxic, molecular and in silico effects of chlorambucil and tamoxifen on 2D/3D MDA-MB-231 and HeLa cancer cell models   
Yazarlar (3)
Durmus Burak Demirkaya
Dr. Öğr. Üyesi Habibe Sema ARSLAN ÜNAL Dr. Öğr. Üyesi Habibe Sema ARSLAN ÜNAL
Kırşehir Ahi Evran Üniversitesi, Türkiye
Prof. Dr. Serap YALÇIN AZARKAN Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Devamını Göster
Özet
This study aimed to investigate the cytotoxic, morphological, and molecular effects of Tamoxifen (TMX) and Chlorambucil (CHL) on breast cancer (MDA-MB-231) and cervical cancer (HeLa) cell lines. The impact of these agents on metastatic behavior, apoptotic mechanisms, and gene expression profiles was examined in both two-dimensional (2D) and three-dimensional (3D) cell culture models. Cells were treated with varying concentrations of TMX and CHL. Cytotoxicity was assessed using the XTT assay, and morphological changes were monitored by microscopy. Migration and invasion assays assessed metastatic potential. VEGFA expression was quantified by qRT-PCR. In 3D cultures, treatment responses were evaluated based on size reduction and structural changes in hydrogel-based spheroids. Docking analysis was conducted to determine binding affinities of TMX and CHL. TMX and CHL exhibited dose-dependent effects on breast and cervical cancer cells. Combination treatment led to significantly greater reductions in cell viability compared to controls (p < 0.05). Moreover, VEGFA expression was markedly reduced in both 2D and 3D models (p < 0.05). These findings support the potential therapeutic value of TMX and CHL. Docking analysis revealed highly negative binding energies, consistent with in vitro results, indicating synergistic interaction at molecular and cellular levels. TMX and CHL combination therapy demonstrated potent anti-cancer activity in breast and cervical cancer models, reducing cell viability, metastatic capacity, and VEGFA expression. These results suggest that TMX and CHL, when used together, may represent a promising strategy for developing synergistic and targeted cancer therapies. Further in vivo and clinical validation is warranted.
Anahtar Kelimeler
Tamoxifen | Chlorambucil | Cytotoxicity | Expression | 2D and 3D models
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı MOLECULAR BIOLOGY REPORTS
Dergi ISSN 0301-4851 Wos Dergi Scopus Dergi
Dergi Grubu Q3
Makale Dili İngilizce
Basım Tarihi 12-2025
Cilt No 53
Sayı 1
DOI Numarası 10.1007/s11033-025-11286-5