Breast Cancer Selective Disruption of Actin Cytoskeleton by Diallyl Trisulfide

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Diallyl trisulfide (DATS) is a phytochemical with demonstrated anti-cancer properties against various solid tumors.
• Previous studies indicated that DATS exhibits resistance to growth inhibition in immortalized mammary epithelial cells (MCF-10A).

Purpose of the Study:

• To investigate the cancer-selective effects of DATS by comparing its impact on a breast cancer cell line (SK-BR-3) and a non-oncogenic cell line (MCF-10A).
• To elucidate the molecular mechanisms underlying DATS's anti-cancer activity, focusing on gene expression and cellular pathway alterations.

Main Methods:

• RNA-sequencing (RNA-seq) analysis was performed on SK-BR-3 and MCF-10A cells treated with DATS.
• Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate gene expression changes.
• Western blotting was employed to assess protein phosphorylation, specifically of dynamin-1-like (DRP1) protein.

Main Results:

• DATS treatment upregulated actin cytoskeleton-associated genes and downregulated mitochondria-related genes in SK-BR-3 cells, but not in MCF-10A cells.
• DATS dose-dependently disrupted the actin cytoskeleton in SK-BR-3 cells, with MCF-10A cells showing greater resistance.
• DATS increased DRP1 phosphorylation in SK-BR-3 cells, though DRP1 deletion did not affect DATS-mediated apoptosis.
• Downregulation of citric acid cycle genes was observed in SK-BR-3 cells upon DATS treatment.

Conclusions:

• The actin cytoskeleton is identified as a novel molecular target of DATS in breast cancer cells (SK-BR-3).
• DATS's disruption of the actin cytoskeleton may contribute to its inhibitory effects on breast cancer cell migration.
• The differential effects of DATS on cancer versus normal mammary cells highlight its potential as a targeted anti-cancer agent.