3. Umbruch 4.4..2005 - Online Pot

Potential use of cannabimimetics in the treatment of cancer 169
Figure 2. Mechanisms for cannabinoid receptor-mediated inhibition of cancer growth and spreading.
The different intracellular signaling pathways implicated in cannabinoid receptor-mediated inhibition
of cancer cell proliferation and metastasis, stimulation of cancer cell apoptosis and inhibition of
endothelial cell proliferation and migration (and hence of angiogenesis) are shown. Under certain conditions,
however, ∆ 9 -THC and anandamide have been found to stimulate either EGFR or androgen
receptor expression, and to lead to enhanced proliferation in vitro of glioma and prostate carcinoma
cells, respectively [26, 27]. AEA, N-arachidonoylethanolamine (anandamide); ANG-2, angioprotein-2;
EGFR, epithelial growth factor receptor; ERK, extracellular signal-regulated kinase; MMP-2,
matrix metalloproteinase-2; NGF, nerve growth factor; p27 (kip1) , cyclin-dependent kinase inhibitor;
PIGF, placental growth factor; PKA, protein kinase A; PKB, protein kinase B; PRL, long form of the
prolactin receptor; Trk, high-affinity neurotrophin receptor; VEGF, vascular endothelial growth factor;
VEGFR-1, vascular endothelial growth factor receptor-1. Adapted from [116].
ro-anandamide, by being suppressed or enhanced in healthy or cancer cells,
respectively. Thus, the degree of CB 1 receptor expression determines the
extent of the responsiveness of normal or transformed FRTL-5 cells to
(endo)cannabinoids [33].
Inhibition of growth factor receptor signaling following CB 1 receptor activation
has been shown also in pheochromocytoma [34], skin carcinoma [35]
and prostate carcinoma cells [36] and is likely to be a general mechanism
underlying the anti-proliferative actions by (endo)cannabinoids (Fig. 2).
However, another molecule involved in cancer cell proliferation by governing
cyclin-dependent kinase 2 activity, and whose over-expression can block the
cell cycle in the G 1 phase during the G 1–S transition, is the p27 protein, which
is also under the negative control of the ras oncogene. Accordingly, met-fluo-