cannabinoid-mediated apoptotic cell death was mediated at least partly by ICAM-1

(Haustein et al. 2014).

All the abovementioned studies favor the role of cannabinoids in inhibiting tumor

growth via activation of apoptotic pathways. In summary, cannabinoid agents may

be considered as potential anti-metastatic drugs.

12.5.5.6 Renal Cell Carcinoma (RCC)

Renal cell carcinoma accounts for 90% of all renal malignancies. RCC treatment is

less effective due to lack of response to conventional therapies. This study shed light

on the use of cannabinoids in treating cancer. Inhibition of proliferation in RCC is

mediated via CB2 receptors. The study conducted on RCC cell lines 786-O (pri-

mary) and ACHN (metastatic) revealed distinct role of cannabinoid receptors in

amelioration of cancer cell progression. In this study, treatment of RCC cell lines

with a nonselective CB1/CB2 receptor agonist (WIN 55,212-2) inhibited cell prolif-

eration significantly. WIN 55,212-2 induced cancer cell death by arresting the cell

cycle in G0/G1 phase. In the same study, no cell death was observed when normal

epithelial cells such as ASE-5063 were exposed to cannabinoid agonists (Khan et al.

2018). This further confirmed that the antiproliferative role of cannabinoids is

confined only to the cancer cells.

12.5.5.7 Gastric Cancer

Effect of cannabinoids has also been observed in gastric cancer. It is suggested that

both the receptors are involved in the inhibition of invasion and metastasis in cancer

cells. In in vitro study on AGS and MKN-1 (gastric cancer cell lines), administration

of WIN 55,212-2 demonstrated the decrease in the expression of MMP-2 and

VEGF-A (Xian et al. 2010). In the study by Oh et al., administration of WIN

55,212-2 (cannabinoid agonist) indicated the antineoplastic effect in an in vivo

model of gastric cancer. Animal model after treatment with WIN 55,212-2-

demonstrated the increase in apoptosis. Downregulation in the expression of

MMPs was observed by the treatment of the cannabinoid agonist. To be specific

this study showed that WIN 55,212-2 downregulated the expression of MMP-2,

MMP-7, and MMP-9, which suggests inhibition in metastasis in gastric cancer

(Oh et al. 2013). Evidences suggested that cannabinoids, in addition to palliative

care in oncology, can inhibit proliferation, angiogenesis, and metastasis.

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