Owing to their ability to self-renew and differentiate, CSCs are capable of regenerating the heterogeneous tumor population after hormone ablation, which accounts for tumor relapse. Therefore, elimination of the bulk of frequently replicating tumor cells as well as the rare subset of slow, dividing stem-like cells that are responsible for tumor regeneration may represent a better therapeutic strategy in the treatment of prostate cancer. The therapeutic properties of the hemp plant, Cannabis sativa, have been known for many years, but the recreational use of its psychoactive effects has restricted its possible pharmaceutical application. In recent years cannabinoids and their derivatives have drawn renewed attention because of their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression.
Cannabinoids have been shown to induce apoptosis in gliomas , PC-12 pheochromocytoma , CHP100 neuroblastoma , and hippocampal neurons in vitro, and most interestingly, regression of C6-cell gliomas in vivo . Plant-derived cannabinoids, especially cannabidiol, are shown to be potent inhibitors of prostate carcinoma both in vitro and in vivo.Our case studies confirmed cannabinoid efficacy in reducing muscle spasticity in multiple sclerosis , pain levels over a 12-month period and Cannabis responsive head injury induced multiple disabilities . To date, cannabinoids have been successfully used in the treatment of nausea and vomiting , two common side effects that accompany chemotherapy in cancer patients. Nevertheless, the use of cannabinoids in oncology might be somehow underestimated since increasing evidence exist that plant, synthetic, and endogenous cannabinoids are able to exert a growth inhibitory action on various cancer cell types. However, mobile vertical rack the precise pathways through which these molecules produce an antitumor effect has not been yet fully characterized, also because their mechanism of action appears to be dependent on the type of tumor cell under study.
It has been reported that cannabinoids can act through different cellular mechanisms, e.g., by inducing apoptosis, cell-cycle arrest, or cell growth inhibition, but also by targeting angiogenesis and cell migration . Furthermore, the antitumor effects of plant, synthetic and endo-cannabinoids can be mediated by activation of either CB1 or CB2 receptors or both . After the discovery of the two specific molecular targets for THC, CB1, and CB2 , it became clear that most of the effects of marijuana in the brain and peripheral tissues were due to activation of these two G-protein-coupled cannabinoid receptors. However, evidence is also accumulating that some pharmacological effects of marijuana are due to Cannabis components different from Tetrahydro-cannabinol. Indeed, C. sativa contains at least 400 chemical components, of which 66 have been identified to belong to the class of the cannabinoids . The main limitation of the possible future use of THC in oncology might be represented by adverse effects principally at the level of the central nervous system, consisting mostly of perceptual abnormalities, occasionally hallucinations . However, most non-THC plant cannabinoids seem to be devoid of direct psychotropic properties. In particular, it has been ascertained that cannabidiol is nonpsychotropic and may even mitigate THC psychoactivity by blocking its conversion to the more psychoactive 11-hydroxy-THC .
Moreover, it has been recently found that systematic variations in its constituents do not affect the behavioral or neurophysiological responses to marijuana . Finally, it has been also shown that, unlike THC, systemic administration to rats of cannabigerol does not provoke poly-spike discharges in the cortical electroencephalogram during wakefulness and behavioral depression . These and other observations reinforce the concept that at least cannabidiol, cannabigerol, and cannabichromene lack psychotropic activity and indicate that for a promising medical profile in cancer therapy, research should focus on these compounds, which so far have been poorly studied with regard to their potential antitumor effects. By keeping this goal in mind, we decided to investigate the antitumor properties of plant cannabis. We screened two distinct chemically characterized Cannabis extracts , where the presence of nonpsychotropic cannabinoids along with THC has been reported to mitigate the potential side effects of the latter compound in clinical trials . Despite research efforts, little is known about the prostatic cancer stem cells which were suggested to play an important role in tumor initiation, progression, and chemoresistance . Because CSCs are believed to contribute to chemoresistance, we reasoned that the chemosensitizing effect of cannabis may be mediated through targeting of prostate CSCs.