R(+)-Methanandamide-Induced Apoptosis of Human Cervical Carcinoma Cells Involves A Cyclooxygenase-2-Dependent Pathway

Abstract

This study demonstrates COX-2 induction and synthesis of L-PGDS-derived, PPARgamma-activating PGs as a possible mechanism of apoptosis by MA.

Cyclooxygenase-2 and tissue inhibitor of matrix metalloproteinases-1 confer the antimigratory effect of cannabinoids on human trabecular meshwork cells

“…With respect to the observed CB receptor dependency of COX-2 expression by both cannabinoids, our data contradict previous observations from our group showing a receptor-independent induction of COX-2 expression by both cannabinoids in human non-pigmented ciliary epithelial [11] and neuroglioma cells [27][28][29]42] and for MA in human cervical carcinoma cells [30]. Thus, dependent on the cell type, cannabinoids may use either receptor-dependent or -independent pathways to confer increased synthesis of A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 20 PGs which may on the one hand depend on extracellular activation of membrane-bound receptors and might otherwise rely on a lipid raft-dependent intracellular uptake [29].…”

“…Based on our previous investigations demonstrating cannabinoids as potent inductors of COX-2 expression in diverse cell types [11,[27][28][29][30][31]] and on the above mentioned interference of NSAIDs with the IOP-lowering action of cannabinoids, we were particularily interested in the role of COX-2 and one of its potential downstream targets, the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), in this process. Here we show that the antimigratory action of the phytocannabinoid THC and the stable endocannabinoid analogue MA on human TM cells is conferred by a COX-2-dependent upregulation of TIMP-1.…”

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

“…Mol Cancer Ther; 12(1) January 2013 Molecular Cancer Therapeutics 70 PPAR-g mRNA levels were determined by real-time reverse transcriptase PCR (RT-PCR) using the TaqMan RNA-to-C T 1-Step Kit and TaqMan Gene Expression Assays (Applied Biosystems) as described (18,19,24).…”

“…In view of the fact that the eicosanoid system has been reported to be involved in biologic effects of cannabinoids (15)(16)(17), we were particularly interested in a possible involvement of COX-2 expression and prostaglandin (PG) synthesis in the proapoptotic action of cannabidiol. In fact, recent studies indicate a COX-2-dependent pathway underlying apoptosis elicited by the cannabinoid compounds anandamide and its analog R(þ)-methanandamide (18,19). In addition, COX-2 upregulation has been reported to be involved in the proapoptotic action of stearoylethanolamide (20), the alkylphospholipids edelfosin and perifosin (21,22), as well as the chemotherapeutics cisplatin, 5-fluorouracil, and paclitaxel (23,24).…”

“…In addition, COX-2 upregulation has been reported to be involved in the proapoptotic action of stearoylethanolamide (20), the alkylphospholipids edelfosin and perifosin (21,22), as well as the chemotherapeutics cisplatin, 5-fluorouracil, and paclitaxel (23,24). About the mechanism underlying COX-2-dependent apoptosis, several studies provided evidence for an activation of the transcription factor PPAR-g by COX-2-dependent PGs of the D-and Jseries (19,(24)(25)(26). This view is further corroborated by investigations indicating a pivotal role of PPAR-g activation in eliciting apoptosis of different tumor cells including non-small cell lung cancer cells (NSCLC; refs.…”