Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies

Area of Science:

• Phytochemistry
• Oncology
• Molecular Biology

Background:

• Estrogen receptor-positive (ER+) breast cancer treatment traditionally relies on aromatase inhibition and ER modulation.
• Emerging drug resistance necessitates novel therapeutic strategies for breast cancer.
• Cannabis sativa contains over 120 phytocannabinoids, with limited research on their therapeutic potential in cancer.

Purpose of the Study:

• To investigate the in silico and in vitro effects of 129 phytocannabinoids on key molecular targets in ER+ breast cancer.
• To identify phytocannabinoids that modulate aromatase, estrogen receptor (ER), and androgen receptor (AR).

Main Methods:

• In silico screening of 129 phytocannabinoids against aromatase, ER, and AR.
• In vitro validation of selected phytocannabinoids' activity on ER and aromatase.
• Assessment of phytocannabinoid interactions as antagonists, agonists, or inverse agonists.

Main Results:

• In silico analysis suggested potential aromatase inhibition and ERα antagonism by certain cannabinoids.
• Nine selected phytocannabinoids demonstrated in vitro potential as ER antagonists with inverse agonist properties or as ER agonists.
• These cannabinoids also exhibited weak aromatase inhibition and AR antagonism with inverse agonist action.

Conclusions:

• This research provides a comprehensive analysis of phytocannabinoid actions on ER+ breast tumor targets.
• Identified phytocannabinoids exhibit therapeutic potential for ER+ breast cancer and potentially other diseases.
• Highlights the largely unexplored therapeutic possibilities of diverse phytocannabinoids in oncology.