Cannabinoids and Cancer

Abstract

Marijuana has been used in medicine for millennia, but it was not until 1964 that delta9-tetrahydrocannabinol (delta9-THC), its major psychoactive component, was isolated in pure form and its structure was elucidated. Shortly thereafter it was synthesized and became readily available. However, it took another decade until the first report on its antineoplastic activity appeared. In 1975, Munson discovered that cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this action was shown to be inhibition of DNA synthesis. Antiproliferative action on some other cancer cells was also found. In spite of the promising results from these early studies, further investigations in this area were not reported until a few years ago, when almost simultaneously two groups initiated research on the antiproliferative effects of cannabinoids on cancer cells: Di Marzo's group found that cannabinoids inhibit breast cancer cell proliferation, and Guzman's group found that cannabinoids inhibit the growth of C6 glioma cell. Other groups also started work in this field, and today, a wide array of cancer cell lines that are affected is known, and some mechanisms involved have been elucidated.

Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo

“…Furthermore, we have shown that THC inhibited the EGF-induced phosphorylation of ERK1/2, JNK1/2 and AKT. Although THC exhibits psychoactive effects mediated by neuronal CB 1 receptors (Piomelli, 2003), the adverse side effects tend to wane with continuous use (Kogan, 2005). Our findings suggest a therapeutic use of cannabinoids like THC in the treatment of EGFRoverexpressing, aggressive and chemotherapy-resistant lung cancers.…”

“…Previous studies have demonstrated tumor-promoting or antineoplastic effects of THC (Munson et al, 1975;Kogan, 2005). However, cannabinoid effects on the EGFR-mediated growth and motility of lung cancer cells have not been characterized to our knowledge.…”

“…THC exhibits equal affinity toward CB 1 and CB 2 , the two G protein-coupled cannabinoid receptors characterized and cloned from mammalian tissues (Matsuda et al, 1990;Munro et al, 1993). THC exerts its various biological activities after engaging these cannabinoid receptors (Hauck et al, 2001) and has had variable antitumor effects in animal and clinical studies (Munson et al, 1975;Kogan, 2005;Guzma´n et al, 2006), yet little is known about its impact on the invasion and growth of NSCLC. In this investigation, we focused our studies on NSCLC, which constitutes the majority of the lung cancer cases.…”

<i>In Vitro</i> Anticancer Activity of Plant-Derived Cannabidiol on Prostate Cancer Cell Lines

“…However, 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 [7] [19]. Furthermore, the antitumor effects of plant, synthetic and endocannabinoids can be mediated by activation of either CB1 [20] or CB2 receptors or both [21] [22].…”

Cannabinoids, the Heart of the Matter

“…This, in turn, suggests a therapeutic potential in the modulation of the ECS. Endocannabinoids and their synthetic analogs have important effects on the cardiovascular system, including complex mechanisms affecting the vasculature and the myocardium, but also autonomic outflow regulation through sites of action in the central and peripheral nervous system 43, 66, 69, 70. Modulation of the ECS has been suggested as a therapeutic avenue for various disorders of the cardiovascular system ranging from atherosclerosis and restenosis, hypertension, cirrhotic cardiomyopathy; to myocardial infarction, and chronic heart failure 42…”