Cancer is a prominent health problem in the world. One in 4 deaths in the United States is due to cancer (Siegel, Miller, & Jemal, 2016). Colorectal cancer represents the fourth most common cancer world- wide, both in men and women, with 95,270 new cases and 49,190 deaths estimated to occur in 2016 (Siegel et al., 2016). Pharmacoeconomic studies have highlighted a trend for rising costs associated with colorectal cancer, which is linked to the increasing use of targeted biological therapies (Kriza, Emmert, Wahlster, Niederländer, & Kolominsky-Rabas, 2013). Screening strategies are utilized but have not reduced disease incidence or mortality (Derry, Raina, Agarwal, & Agarwal, 2013). Furthermore, therapeutic intervention, which is by itself very toxic, may fail to prevent disease progression to metastatic disease (Ebos & Kerbel, 2011). Therefore, there is an interest in both cancer preventive strategies – which include experimentation with safe phytochemical agents – and new curative treatments (Franceschi & Wild, 2012) (Romano et al., 2014).
Recent progress in plant biotechnology has made possible the cultivation of Cannabis chemotypes rich in specific phytocannabinoids, from which standardized extracts, containing known amounts of phytocannabinoids, may be obtained (Russo, 2011). The best studied among these extracts is generally referred as cannabidiol (CBD) botanical drug substance (CBD BDS, that is a standardized Cannabis extract with high content of CBD) (Romano et al., 2014).
Romano et al. found that CBD BDS and CBD reduced cell proliferation in tumoral cells, but not in normal healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1 -sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer (Romano et al., 2014).
They concluded that CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis- based medicines in cancer patients (Romano et al., 2014).
Sreevalsan’s research group proposed a different hypothesis of how CBD exerts its anticancer effects, and found that cannabinoids induce mRNA expression of several phosphatases, and this is consistent with other phytochemical anticancer drugs (Aggarwal, Vijayalekshmi, & Sung, 2009; Ahn et al., 2008; Lee, Hahm, & Singh, 2010; Pandey, Sung, & Aggarwal, 2010; Pathak et al., 2007; Yu et al., 2008). The results obtained using the phosphatase inhibitor SOV demonstrate that induction of apoptosis by WIN and CBD was significantly blocked by the phosphatase inhibitor SOV, and this represents a novel proapoptotic pathway induced by cannabinoids (Sreevalsan, Joseph, Jutooru, Chadalapaka, & Safe, 2011).
Another group (Aviello et al., 2012) found in colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cancer cell proliferation in a CB1-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms (Aviello et al., 2012).
Tumour cell migration and adhesion constitute essential features of metastasis in colon cancer. .In line with this work, Kargl et al. noted that G-protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. They investigated the involvement of GPR55 in migration and metastasis of colon cancer cells (Kargl, Andersen, Hasenöhrl, Feuersinger, & Stan, 2016).
Adhesion and migration assays using the highly metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis were performed. The GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells. They concluded that GPR55 is involved in the migratory behaviour of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis (Kargl et al., 2016).
As time progresses, more research is being conducted to understand the role of CBD in cancer cell growth and metastasis, and CBD continues to be a compound of interest in the fight against cancer.
References:
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