The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

Abstract

Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

“…First, it cannot be excluded that key players of cannabidiol's antitumorigenic effects reported for other experimental systems may also be part of cannabidiol's proapoptotic impact on lung cancer cells. Accordingly, cannabidiol was shown to elicit intrinsic apoptotic pathways via elevation of reactive oxygen species in diverse cancer cell types (3)(4)(5)7) and to activate autophagic signaling pathways (6).…”

“…As the clinical use of cannabinoids is limited by their adverse psychotropic side effects, the interest in the nonpsychoactive Cannabis-derived compound cannabidiol as potential systemic cancer therapeutic has substantially increased in recent years. In fact, cannabidiol has been shown to elicit pronounced proapoptotic or autophagic effects on different types of tumor cells (3)(4)(5)(6)(7). In a panel of tumor cell lines, cannabidiol even exhibited the most potent antiproliferative action as compared with a variety of other cannabinoids (3).…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…It dampens nitric oxide (NO) production in animal models of acute and chronic inflammation (24,152,162,247,267,600,654,758), the expression of inflammatory cytokines and transcription factors [interleukin (IL)-1␤, IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-␣, interferon (IFN)-␥, CCL3, CCL4, NF-B] (39, 419), and reactive oxygen species (ROS) production (320, 767). However, in many types of cancer cells, CBD is capable of generating ROS, thereby inducing cytotoxicity or apoptosis and autophagy (478,540,543,547,552,610,862). CBD also improves mithochondrial function and enhances mithochondrial biogenesis in vivo under pathological conditions (327).…”

A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma

“…Of interest, at least one of these components, namely, cannabinol (CBD; Supplementary Fig. 1), has been shown to reduce the growth of different types of tumor xenografts including gliomas (20)(21)(22)(23)(24)(25). Although the mechanism of CBD antitumoral action has not been completely clarified yet, it has been proposed that CBD-induced apoptosis relies on an increased production of reactive oxygen species (ROS; ref.…”