Julie Gardener
New Member
Cannabinoid receptor-1 modulation induces apoptosis of human melanoma cells
AbstractArachidonic acid metabolizing enzymes including COX and LOX are expressed in melanoma cells producing an array of bioactive lipids including endocannabinoids. These lipids act through their cognate G-protein coupled receptors, CB1/CB2. There are reports in the literature that various human cancers express CB1 receptor and CB1 agonists inhibit proliferation and induce apoptosis of various cancer types. Malignant melanoma is derived from neuroectodermal melanocytes and may preserve such geno- or phenotype including cannabinoid receptors. Microarray studies on human melanoma cell lines versus nevus cells revealed expression of CB1 receptor in human melanoma cells of various metastatic potential which was confirmed by nested PCR and direct sequencing. Immunocytochemistry revealed that CB1 receptor can be detected at the cell surface, in the cytoplasm (frequently associated with cytoskeleton) and interestingly in the nucleus using confocal microscopy. Both CB1 receptor agonist, Met-F-AEA as well as the CB1 receptor inhibitor, AM251 inhibited proliferation of human melanoma cells in vitro with an IC50 of appr. 5 µM. Furthermore, CB1 antagonist, AM251, induced massive apoptosis (up to 50%) of human melanoma cell lines with a similar IC50 (4-7 µM). Melanoma cells are characterized by constitutive resistance to apoptosis resulting in resistance to various chemotherapeutics. Pharmacological modulation of CB1 receptor in melanoma can be regarded as a novell approach to suspend apoptosis resistance. This work was supported by the Ministry of Economy (NKFP1a-0024-05)
Source: Cannabinoid receptor-1 modulation induces apoptosis of human melanoma cells -- Timar et al. 2008 (1): 2678 -- AACR Meeting Abstracts
