Identification of plant extracts sensitizing breast cancer cells to TRAIL

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and high recurrence rates.
• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cancer cell death but faces resistance, limiting its clinical efficacy.
• Developing combination therapies is crucial to enhance TRAIL efficacy and overcome resistance mechanisms in TNBC.

Purpose of the Study:

• To identify medicinal plant extracts that can synergize with TRAIL therapy.
• To evaluate the efficacy of plant extracts in overcoming TRAIL resistance in TNBC cell lines.
• To investigate the molecular mechanisms underlying the synergistic effects of plant extracts and TRAIL.

Main Methods:

• Screening of 138 medicinal plant extracts against TRAIL-sensitive and -insensitive TNBC cell lines (MDA-MB-231, MDA-MB-468).
• Assessing cytotoxicity of single-agent plant extracts and their combination with TRAIL.
• Investigating the effect of promising plant extracts on p65 phosphorylation, a key TRAIL-resistance pathway.

Main Results:

• Five plant extracts (Uvaria dac, Artemisia vulgaris, Cortia depressa, Dichasia bengalensis, Cinnamomum obtusifolium) demonstrated significant synergistic effects with TRAIL without substantial single-agent cytotoxicity.
• Uvaria dac, Artemisia vulgaris, and Cinnamomum obtusifolium suppressed p65 phosphorylation, a mechanism implicated in TRAIL resistance.
• These extracts showed efficacy against both TRAIL-sensitive and -insensitive TNBC cell lines.

Conclusions:

• The identified plant extracts, when combined with TRAIL, hold potential for improving therapeutic outcomes in TNBC patients.
• These natural compounds may offer a strategy to overcome primary or acquired resistance to TRAIL therapy.
• Further research into these combinations could lead to novel clinical applications for treating aggressive breast cancer subtypes.