A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner

Area of Science:

• Natural Products Chemistry
• Cancer Biology
• Molecular Oncology

Background:

• Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective treatments.
• Natural compounds offer potential therapeutic avenues for cancer, necessitating exploration of plant-derived molecules.
• The role of TP53 and its associated microRNAs in HCC progression requires further elucidation.

Purpose of the Study:

• To investigate the anti-cancer effects of flavonoids isolated from Cleome droserifolia on HCC cell lines.
• To determine the impact of these flavonoids on TP53 expression and its downstream tumor suppressor microRNAs.
• To identify specific compounds with potent inhibitory activity against HCC progression.

Main Methods:

• Isolation and characterization of three flavonol glycosides from Cleome droserifolia.
• In vitro assessment of cellular viability, anchorage-independent growth, and migration in HCC cell lines (HepG2).
• Analysis of TP53 and tumor suppressor microRNA (miR-15a, miR-16, miR-34a) expression levels following treatment.

Main Results:

• Isolated compounds demonstrated a dose- and time-dependent reduction in HCC cell viability and growth.
• Compound (2) exhibited the most significant inhibition of HCC tumorigenic activity (IC50 = 36 ± 1.70 µM) and proliferation.
• Compound (2) restored TP53 and tumor suppressor miRNAs (miR-15a, miR-16), with effects attenuated by anti-miR-15a and anti-miR-16.

Conclusions:

• Cleome droserifolia flavonoids possess significant in vitro anti-cancer properties against HCC.
• Compound (2) is a potent inhibitor of HCC progression, potentially acting through the TP53/miR-15a/miR-16 pathway.
• This study suggests a novel therapeutic role for Cleome droserifolia in managing HCC progression.