Javid Farideh A, Phillips Roger M, Afshinjavid S, Verde Roberta, Ligresti Alessia
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Eur J Pharmacol. 2016 Mar 15;775:1-14. doi: 10.1016/j.ejphar.2016.02.010. Epub 2016 Feb 5.
Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.
大麻素已被使用了许多世纪来缓解疼痛,在过去十年中,内源性大麻素系统与多种病理生理状况有关,如情绪和焦虑障碍、帕金森病和亨廷顿病等运动障碍、神经性疼痛、多发性硬化症、脊髓损伤、动脉粥样硬化、心肌梗死、中风、高血压、青光眼、肥胖症和骨质疏松症。多项研究表明,大麻素还具有抗癌活性,而且由于大麻素通常耐受性良好,不会产生传统化疗的典型毒性作用,因此开发大麻素作为潜在的抗癌疗法具有相当大的价值。虽然大麻素的精神活性作用可能会阻碍该领域的任何进展,但最近的研究表明,大麻素的非精神活性成分在激活凋亡途径、诱导抗增殖和抗血管生成作用方面具有价值。上述作用被认为是通过细胞外信号调节激酶(ERK)、蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)途径、磷酸肌醇3激酶(PI3K)途径和缺氧诱导因子1(HIF1)等途径实现的,所有这些都是癌症特征的重要促成因素。许多重要问题仍然没有答案或未得到充分解决,因此需要在基础临床前和临床水平上进行进一步研究。在本综述中,我们探讨这些问题,以期确定未来研究需要解决的关键挑战。