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

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Breast cancer proliferation and apoptosis are critical mechanisms in tumor development.
• The precise mechanisms of tri-chalcone's antiproliferative and apoptotic effects on breast cancer remain largely unelucidated.
• Previous research indicates tri-chalcones can inhibit MCF-7 breast cancer cell proliferation.

Purpose of the Study:

• To investigate the effects of tri-chalcone compounds on targets involved in antiproliferative and apoptosis pathways in breast cancer.
• To elucidate the molecular mechanisms by which tri-chalcone S1-2 suppresses MCF-7 cell proliferation and induces apoptosis.

Main Methods:

• Bioinformatics analysis to identify apoptosis target receptors.
• In vitro evaluation using tri-chalcone-treated MCF-7 cells.
• Molecular dynamics (MD) simulations to assess compound-protein interactions and flexibility.
• Gene expression analysis to determine the impact on apoptosis-related genes.

Main Results:

• Tri-chalcones were found to interact with six apoptosis targets: TNFα, Bak, Bcl-2, caspase-9, and caspase-8.
• Tri-chalcone S1-2 demonstrated the strongest binding affinities for TNFα, caspase-8, caspase-9, Bcl-2, and Bak.
• MD simulations showed minimal flexibility for S1-2-protein complexes.
• Tri-chalcone S1-2 significantly inhibited MCF-7 cell proliferation (IC50 = 5.31 µg/mL) and induced apoptosis (43.80%).
• S1-2 treatment upregulated TNFα, Bak, caspase-8, and caspase-9, while downregulating Bcl-2 in MCF-7 cells.

Conclusions:

• Tri-chalcone S1-2 effectively suppresses MCF-7 breast cancer cell proliferation and induces apoptosis.
• The compound acts through both intrinsic and extrinsic apoptosis pathways, modulating key target proteins.
• This study provides a deeper understanding of tri-chalcone's therapeutic potential in breast cancer treatment.