P0112 Cannabidiol (CBD) targeting of colorectal cancer cells is mutation-independent and via CB2 receptor
M Moniruzzaman, T Janjua, J Begun, A PopatAbstract
Background
Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties including anti-epileptic and anti-inflammatory activity. Several in vitro and in vivo studies have shown that CBD has antitumour potential against colorectal cancer (CRC), the third deadliest cancer in the world. However, as different mutations influence the antitumour effects and CBD can bind a variety of receptors, it is yet to be determined whether specific CRC mutations affect CBD’s efficacy in treatment of CRC.
Methods
To investigate this, we selected four CRC cell lines, including HCT116, HT-29, LS174T, and LS153 which harbour distinct mutations. Cells were treated with a range of concentrations of CBD to evaluate its cytotoxic effects and impact on cell proliferation, migration, and invasion using a live-cell imaging system. IC50 values were then calculated for each parameter. The level of endoplasmic reticulum (ER) stress pathway markers was also measured using qRTPCR. The requirements for CB1 or CB2 receptor-medicated signalling was investigated using the selective inhibitors AM251 and SR144528, respectively.
Results
Our results demonstrate that CBD induces apoptosis and halts proliferation, migration, and invasion of CRC cells in a concentration dependent manner. CBD showed potent antitumour effects in the tested cell lines with no obvious effect of different mutations such as KRAS, BRAF, APC, PTEN etc. CBD also induced ER stress in CRC cells but not the healthy intestinal organoids. Co-treatment with SR144528 inhibited the effects of indicating involvement of CB2 receptor activation in the anticancer effects of CBD.
Conclusion
Together, these results demonstrated that CBD could be effective for CRC regardless of the underlying mutation through CB2 receptor activation.