Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect

Abstract

In the present study, we found that CBD inhibited U87-MG and T98G cell proliferation and invasiveness in vitro and caused a decrease in the expression of a set of proteins specifically involved in growth, invasion and angiogenesis. In addition, CBD treatment caused a dose-related down-regulation of ERK and Akt prosurvival signaling pathways in U87-MG and T98G cells and decreased hypoxia inducible factor HIF-1α expression in U87-MG cells. Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways. As CBD is a non-psychoactive phytocannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anti-cancer drug in the management of gliomas.

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

“…Activation of MMPs may be involved in tumor progression and metastasis formation, which is inhibited by CBD, likewise the NF-κB signaling. Furthermore, CBD by itself has been reported to have antitumor effects in a large variety of cancer cell lines, as well as in some explanted tumor models (44)(45)(46), which would rather predict a synergistic effect with antineoplastic drugs. In fact, Insys Therapeutics just received FDA orphan drug designation for CBD as a potential treatment for glioblastoma multiforme in humans.…”

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

“…Both cannabinoids can reduce cell numbers by inhibiting cell-cycle progression and cell growth as well as by triggering apoptosis and engaging autophagy (19), and are also antiangiogenic and antimigratory (15). The two compounds have also been combined in a preparation that is currently licensed to treat multiple sclerosis, which is now undergoing trials in patients with glioma.…”

“…This suggests that receptor activation by some of the cannabinoids may not be a requisite for anticancer activity (3), which highlights the possibility of using cannabinoids in a way that maximizes the anticancer action while simultaneously minimizing psychoactivity (11). In particular, the evidence of the anticancer activity of CBD has grown steadily these past few years (11)(12)(13)(14)(15). These studies have involved its use as a single agent or in combination with other cannabinoids or other treatment modalities, and have included a number of cancer types (5).…”

Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture

“…It is important to emphasize that the lipophilic nature of CBD triggers biologic responses that are independent of protein-mediated mechanisms, including rapid changes in both membrane lipid raft and cholesterol metabolism when applied at 5-20 mM (Ligresti et al, 2006;Rimmerman et al, 2011Rimmerman et al, , 2013. Additional examples of the protein-independent mechanism of CBD include increases in oxidative stress resulting in apoptosis, DNA damage, and autophagy in breast cancer cells (Shrivastava et al, 2011) and in glioma cells (Bisogno et al, 2001;Massi et al, 2004;Solinas et al, 2013;Soroceanu et al, 2013) when this compound is applied at 5-40 mM. Thus, there is a wide range of protein-dependent and protein-independent biologic activities induced by CBD applied in the micromolar range.…”

“…It has been shown that cannabidiol (CBD) exhibits antineoplastic activity in multiple GBM cell lines in culture and in xenograft mouse models (Massi et al, 2004(Massi et al, , 2006(Massi et al, , 2008Vaccani et al, 2005;Marcu et al, 2010;Torres et al, 2011;Nabissi et al, 2013;Solinas et al, 2013;Soroceanu et al, 2013). This antineoplastic activity is mediated through plasma membrane-associated receptors, including G protein-coupled receptor (GPR) 55 and transient receptor potential cation channel subfamily V member (TRPV) 1/2, and involves the production of reactive oxygen as well as induction of autophagy and apoptosis (Bisogno et al, 2001;Ligresti et al, 2006;Massi et al, 2006;Ford et al, 2010;Ramer et al, 2010;Yamada et al, 2010;Piñeiro et al, 2011;Anavi-Goffer et al, 2012).…”