Perspectives in Pharmacology Antitumorigenic Effects of Cannabinoids beyond Apoptosis

According to the World Health Organization, the cases of death caused by cancer will have been doubled until the year 2030. By 2010, cancer is expected to be the number one cause of death. Therefore, it is necessary to explore novel approaches for the treatment of cancer. Over past years, the antitumorigenic effects of cannabinoids have emerged as an exciting field in cancer research. Apart from their proapoptotic and antiproliferative action, recent research has shown that cannabinoids may likewise affect tumor cell angiogenesis, migration, invasion, adhesion, and metastasization. This review will summarize the data concerning the influence of cannabinoids on these locomotive processes beyond modulation of cancer cell apoptosis and proliferation. The findings discussed here provide a new perspective on the antitumorigenic potential of cannabinoids. Cannabinoids are currently used in cancer patients to palliate wasting, emesis, and pain. In addition, evidence has been accumulated over the last decade to suggest that these compounds could also be useful for the inhibition of tumor cell growth by modulating several survival pathways. Although anticancer effects of cannabinoids were shown as early as 1975 in Lewis lung carcinoma (Munson et al., 1975), interest in anticarcinogenic properties of these compounds was even renewed after the discovery of the cannabinoid system and the cloning of specific Gi/o-coupled cannabinoid receptors CB1 and CB2 (De Petrocellis et al., 1998; for review, see also Howlett et al., 2002; Abood, 2005). Although the majority of effects of cannabinoids are mediated via CB1 and CB2, the transient receptor potential vanilloid type 1 (TRPV1) has been described as an additional receptor target for several cannabinoids (Zygmunt et al., 1999; Costa et al., 2004; Ligresti et al., 2006). Finally, there are also various cannabinoid effects that have been associated with molecular events independent of either CB1/CB2 or TRPV1 activation (Ruiz et al., 1999; Hinz et al., 2004; Vaccani et al., 2005; Fogli