A Virtual Drug Discovery Screening Illuminates Campesterol as a Potent Estrogen Receptor Alpha Inhibitor in Breast Cancer

Breast cancer remains a global health challenge, and
innovative
strategies are required to target estrogen receptor α (ERα),
a key player in its development. This study investigates the potential
of campesterol, a natural phytosterol, as an ERα inhibitor for
breast cancer. Our approach integrates in silico, in vitro, and ex vivo experiments to assess
the therapeutic potential of campesterol. In silico analyses highlight campesterol as a promising ERα ligand with
favorable binding affinities and dynamic properties. Structural analysis
reveals conformational changes in ERα upon campesterol binding. In vitro studies confirm the selective growth inhibition
of campesterol against ERα-positive breast cancer cells. This
study extends to ER+ breast cancer patient-derived organoids (PDOs),
showing the effectiveness of campesterol in ERα-positive breast
cancer PDOs. Importantly, it emphasizes the receptor-specific nature
of campesterol, providing insights into its context-dependent action.
In conclusion, campesterol displays potential as an ERα inhibitor,
offering new avenues for ER+ breast cancer treatment.