Novel therapeutic applications for cannabinoids in cancer treatment
Walter Milano, Mario Tecce, Anna Capasso
The endocannabinoid system, comprising the cannabinoid receptors type 1 (CB1) and type 2 (CB2), their endogenous ligands (endocannabinoids), and the proteins that regulate endocannabinoid biosynthesis and degradation, controls several physiological and pathological functions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to both in vitro and in vivo anti-tumor effects. Also, the endogenous ligand arachidonoyl ethanolamide (anandamide; AEA) inhibits the proliferation of human breast cancer cells by blocking the G0/G1-S-phase transition of the cell cycle through interference with cannabinoid CB1 receptor-coupled signal-transducing events. The present review shows that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues. Furthermore, the novel therapeutic applications of cannabinoids in cancer, described here, strongly support the idea that cannabinoids may induce beneficial effect in cancer treatment.
The endocannabinoid system is an almost ubiquitous signalling system involved in the control of cell fate. Recent studies have investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth. The endocannabinoids have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell signalling pathways. In previous studies, we reported that stimulation of cannabinoid CB1 receptors by the metabolically stable endocannabinoid analogue Met-F-AEA inhibits apex ras activity, prevents proliferation of v-K-ras-transformed rat thyroid cells both in vitro and in vivo and is also able to block the growth of already established tumors.
Indeed, our very recent data show that Met-F-AEA significantly inhibits, in tumors as well as in transformed cells, the expression of the vascular endothelial growth factor (VEGF). The levels of the cyclin-dependent kinase inhibitor p27, which is down-regulated by p21ras, were instead increased by Met-F-AEA. All these effects were antagonized by the selective CB1 receptor antagonist SR141716A. Met-F-AEA inhibited in vitro the growth of a metastasis-derived thyroid cancer cell line more potently than a primary cancer cell line. Met-F-AEA significantly reduced the number and size of metastatic nodes in an animal model of metastatic spreading (formation of lung nodules after inoculation of 3LL cells), in a way antagonized by SR141716A. Therefore, the present review indicated that cannabinoids exert their anti-cancer effects in a number of ways and variety of tissues to:
- Stop cells from dividing
- Prevent new blood vessels from growing into tumors
- Trigger cell death, through a mechanism called apoptosis
- Reduce the chances of cancer cells spreading through the body, by stopping cells from moving or invading neighboring tissue
- Speed up the cell’s internal ‘waste disposal machine’ – a process known as autophagy – which can lead to cell death
The novel therapeutic application of cannabinoids in cancer treatment strongly suggest that cannabinoids may induce beneficial effect in cancer treatment.
The endocannabinoid system is an almost ubiquitous signalling system involved in the control of cell fate. Recent studies have investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth. The endocannabinoids have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell signalling pathways. In previous studies, we reported that stimulation of cannabinoid CB1 receptors by the metabolically stable endocannabinoid analogue Met-F-AEA inhibits apex ras activity, prevents proliferation of v-K-ras-transformed rat thyroid cells both in vitro and in vivo and is also able to block the growth of already established tumors.
Indeed, our very recent data show that Met-F-AEA significantly inhibits, in tumors as well as in transformed cells, the expression of the vascular endothelial growth factor (VEGF). The levels of the cyclin-dependent kinase inhibitor p27, which is down-regulated by p21ras, were instead increased by Met-F-AEA. All these effects were antagonized by the selective CB1 receptor antagonist SR141716A. Met-F-AEA inhibited in vitro the growth of a metastasis-derived thyroid cancer cell line more potently than a primary cancer cell line. Met-F-AEA significantly reduced the number and size of metastatic nodes in an animal model of metastatic spreading (formation of lung nodules after inoculation of 3LL cells), in a way antagonized by SR141716A. Therefore, the present review indicated that cannabinoids exert their anti-cancer effects in a number of ways and variety of tissues to:
- Stop cells from dividing
- Prevent new blood vessels from growing into tumors
- Trigger cell death, through a mechanism called apoptosis
- Reduce the chances of cancer cells spreading through the body, by stopping cells from moving or invading neighboring tissue
- Speed up the cell’s internal ‘waste disposal machine’ – a process known as autophagy – which can lead to cell death
The novel therapeutic application of cannabinoids in cancer treatment strongly suggest that cannabinoids may induce beneficial effect in cancer treatment.
https://www.oatext.com/novel-therapeutic-applications-of-cannabinoids-in-cancer-disease.php
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