12.5.5.4 Glioma

Glioma represents 40% of all brain tumors with less survival rate. Many studies have

demonstrated the potential of cannabinoids as antiproliferative agents in vitro and

in vivo.

Glioma cell lines SF126, U87-MG, U251, SF188, and U373-MG after adminis-

tration of THC and WIN 55,212-2 decrease the survival of these cells (McAllister

et al. 2005). Treatment with synthetic cannabinoid WIN 55,212-2 causes

downregulation of Akt and Erk1/2 kinase signaling, inhibits proliferation, and

induces apoptosis. A decrease of mitogenic/pro-survival signaling precedes reduc-

tion of phosphorylation of the proapoptotic protein BAD which then translocates to

the mitochondrial membrane initiating apoptosis.

In vivo study on U87 and U373 cell lines induced animal models after treatment

with CBD exerts antiproliferative effects (Massi et al. 2004). Another study that

supported the role of cannabinoids in apoptosis was conducted by Sanchez et al. In

this study JWH-133 initiates apoptosis via ceramide synthesis de novo and ERK

activation (Sánchez et al. 2001).

Therefore, it can be concluded from the available literature that cannabinoids

demonstrate potent antiproliferative activity in glioma and which can be evaluated

further in other solid cancers as well.

12.5.5.5 Lung Cancer

Non-small cell lung cancer (NSCLC) is considered as one of the most aggressive

solid tumor types. Patients with lung cancer still have an unfavorable prognosis with

<15% 5-year survival rate. Many recent studies have showed that cannabinoids can

act as an effective anticancer agent against NSCLC. In established NSCLC cell lines

H358, A549, and H460, cannabinoid (CBD) exerts anti-invasive property through

CB1 and CB2 receptors and TRPV1 (transient receptor potential cation channel

subfamily member 1/vanilloid) receptor. Studies have also elucidated the role of

TIMP-1 (tissue inhibitor of metalloproteinases)-dependent apoptotic death of

NSCLC cells which is mediated through CB1 and CB2 receptors and TRPV1-

dependent ICAM-1 (Intercellular Adhesion Molecule 1) (Ramer et al. 2012).

Another study showed that the downregulation of CB2 receptors in A549 and

H1299 (lung cancer cell lines) decreased the proliferation, invasion, and migration

and also induced apoptotic cell death. Collectively, these reports have suggested

pro-oncogenic role of CB2 receptors in the progression of NSCLC by regulation of

Bcl-2/Bax axis and caspase cascade activation. THC inactivated the phosphorylation

of ERK1/2, AKT, and JNK1/2. CBD also increased susceptibility toward

lymphokine-activated killer (LAK) cell-mediated cancer cell lysis (Preet et al.

2008; Haustein et al. 2014).

Further in the same study, when xenograft model of metastatic lung cancer was

treated with CBD, the authors observed significant decrease in the lung cancer

nodules. Interestingly, effect of CBD was found to be completely reversed by a

neutralizing antibody to ICAM-1. These observations were enough to suggest that

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