| Yazarlar (5) |
Dr. Öğr. Üyesi Sevinç AKÇAY
Kırşehir Ahi Evran Üniversitesi, Türkiye |
Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye |
Doç. Dr. Selin ÖZKAN KOTİLOĞLU
Kırşehir Ahi Evran Üniversitesi, Türkiye |
Doç. Dr. Sibel ÇELİK
Kırşehir Ahi Evran Üniversitesi, Türkiye |
Bayram Furkan Coskun
|
| Özet |
| The widespread use of pesticides such as deltamethrin (a pyrethroid) and acetamiprid (a neonicotinoid) has sparked concerns regarding their effects on human health, particularly their potential role in carcinogenesis. This study investigated the cytotoxic, molecular, and functional effects of these pesticides, individually and in combination, on the MDA-MB-231 triple-negative breast cancer (TNBC) cell line. This model was chosen to specifically investigate estrogen recpetor (ER)-independent mechanisms due to its expression of targets such as aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor gamma (PPARγ), and G protein-coupled estrogen receptor (GPER); however, it does not reflect normal mammary cell responses. Cytotoxicity was assessed via XTT assays, migration was analyzed using wound-healing assays, and gene expression changes in AhR, PPARγ, and Caspase-3 were measured using RT-qPCR. Molecular docking was performed to predict pesticide-protein interactions, and in silico toxicity assessments using ProTox-II supplemented the in vitro results by predicting toxicity profiles relevant to public health. Both pesticides exhibited dose-dependent cytotoxicity, and their combination produced an additive effect on cell viability. Importantly, suppression of cell migration and downregulation of AhR and PPARγ expression reflected toxic stress responses at high pesticide concentrations, rather than therapeutic or anti-cancer potential. While apoptosis-related gene expression (Caspase-3) was increased, this effect did not reach statistical significance. Molecular docking supported strong interactions with key pathways related to xenobiotic metabolism and apoptosis. These findings emphasize that, at high and non-environmentally relevant concentrations, deltamethrin and acetamiprid induce additive cytotoxic effects and disrupt molecular processes in a mechanistic cancer model. The results highlight the need for further investigation using normal cell systems and environmentally relevant exposures to clarify real-world risk and biological mechanisms, and should not be interpreted as evidence of therapeutic activity. This study underscores the mechanistic relevance of pesticide exposure in environmental toxicology rather than any potential therapeutic application. |
| Anahtar Kelimeler |
| Deltamethrin | Acetamiprid | |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN |
| Dergi ISSN | 0920-654X Wos Dergi Scopus Dergi |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 11-2025 |
| Cilt No | 39 |
| Sayı | 2 |
| Doi Numarası | 10.1007/s10822-025-00697-y |
| Atıf Sayıları |
