A new study found that cannabidiol (CBD) reduced the expression of a key receptor that drives HER2-positive breast cancer while activating cellular stress pathways and increasing cancer cell death. The effects were also examined when CBD was combined with the breast cancer drug trastuzumab.
The study, accepted for publication August 10 in BMC Complementary Medicine and Therapies, was conducted by researchers from Ondokuz Mayıs University in Turkey. Researchers examined SKBR3 human breast cancer cells, which overexpress human epidermal growth factor receptor 2 (HER2), a protein associated with cancer cell growth and survival.
Researchers treated the cells with CBD at concentrations of 9.38, 18.75 and 37.5 micromolar (µM), trastuzumab at 62.5 micrograms per milliliter, or combinations of trastuzumab with either 18.75 or 37.5 µM CBD. Cell proliferation was monitored for 72 hours, while gene expression and apoptosis were assessed after treatment.
CBD produced a dose-dependent reduction in cancer cell proliferation. At 72 hours, 18.75 and 37.5 µM CBD significantly reduced the cell index compared with untreated cells, while the lowest dose did not produce a significant change. When 18.75 µM CBD was combined with trastuzumab, the antiproliferative effect was significantly greater than with either treatment alone. At the higher 37.5 µM CBD concentration, adding trastuzumab did not significantly improve the effect compared with CBD alone.
One of the study’s most notable findings involved HER2 itself. CBD significantly reduced HER2 gene expression at all three concentrations, with expression falling to 88%, 73% and 69% of control levels as the CBD dose increased. Trastuzumab alone did not significantly alter HER2 gene expression. The CBD-trastuzumab combinations also significantly reduced HER2 expression, an effect researchers said appeared to be driven primarily by CBD.
The treatments also activated multiple components of the endoplasmic reticulum (ER) stress response, a cellular process that can lead to apoptosis when stress becomes prolonged or severe. CBD, trastuzumab and their combinations increased expression of major ER stress markers, including PERK, IRE1 and ATF6, along with downstream genes associated with cell death.
Flow cytometry confirmed that CBD, trastuzumab and the combination treatments significantly increased apoptosis while reducing cell viability. Researchers said the results support the possibility that ER stress-mediated apoptosis contributes to CBD’s antiproliferative effects against HER2-positive breast cancer cells.
The researchers conclude that CBD may warrant further investigation both as a potential treatment and in lower-dose combinations with trastuzumab. However, they said additional preclinical and clinical research is needed to establish safety and effectiveness before any potential use in patients.
