Tri-chalcone suppressed breast cancer cell proliferation and induced apoptosis through intrinsic and extrinsic pathways.

Autor: Ismail NZ; School of Chemical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia., Khairuddean M; School of Chemical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia. melati@usm.my., Al-Anazi M; Department of Chemistry, Faculty of Science, University of Tabuk, 71491, Tabuk, Kingdom of Saudi Arabia., Arsad H; Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Penang, Malaysia.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Nov; Vol. 397 (11), pp. 8993-9006. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1007/s00210-024-03220-6
Abstrakt: Breast cancer development depends critically on antiproliferative and apoptotic mechanisms. However, the mechanisms underlying the antiproliferative and apoptosis effects of breast cancer treated with tri-chalcone remain unclear. Tri-chalcones have been demonstrated in prior studies to inhibit the proliferation of breast cancer cells (MCF-7). Following the discovery, this study seeks to investigate the effect of tri-chalcone compounds on targets involved in antiproliferative and apoptosis mechanisms. In this study, we employed bioinformatics analysis along with in vitro evaluation using tri-chalcone-treated MCF-7 cells to determine the responses of antiproliferative and apoptosis mechanisms. The analysis revealed that the compounds interact with six apoptosis target receptors: TNFα, Bak, Bcl-2, caspase-9, and caspase-8. Tri-chalcone S1-2 exhibited the strongest binding affinities for TNFα (-7.39 kcal/mol), caspase-8 (-8.43 kcal/mol), caspase-9 (-8.53 kcal/mol), Bcl-2 (-8.51 kcal/mol), and Bak (-7.15 kcal/mol). The tri-chalcone S1-2 paired with the corresponding proteins showed minor flexibility and extremely small changes of less than 0.25 nm during the MD simulation. Additionally, tri-chalcone S1-2 had a significant inhibitory effect on the proliferation of MCF-7 cells (5.31 ± 0.26 µg/mL) compared to other compounds. S1-2 also induced apoptosis, affecting nearly half (43.80%) of the total early and late apoptosis in MCF-7 cells. S1-2-treated MCF-7 cells also demonstrated upregulations of genes TNFα (1.50), Bak (1.42), caspase-8 (1.24), and caspase-9 (1.61), accompanied by a downregulation of gene Bcl-2 (0.71). The discovery gives us a better understanding of how tri-chalcone S1-2 suppressed MCF-7 cell proliferation and induced apoptosis through intrinsic and extrinsic pathways.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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