PDF(Pubmed)
Abstract：
A glioma is a type of tumor that acts on the Central Nervous System (CNS) in a highly aggressive manner. Gliomas can occasionally be inaccurately diagnosed and treatments have low efficacy, meaning that patients exhibit a survival of less than one year after diagnosis. Due to factors such as intratumoral cell variability, inefficient chemotherapy drugs, adaptive resistance development to drugs and tumor recurrence after resection, the search continues for new drugs that can inhibit glioma cell growth. As such, analogues of endocannabinoids, such as fatty acid amides (FAAs), represent interesting alternatives for inhibiting tumor growth, since FAAs can modulate several metabolic pathways linked to cancer and, thus, may hold potential for managing glioblastoma. The aim of this study was to investigate the in vitro effects of two fatty ethanolamides (FAA1 and FAA2), synthetized via direct amidation from andiroba oil (Carapa guianensis Aublet), on C6 glioma cells. FAA1 and FAA2 reduced C6 cell viability, proliferation and migratory potential in a dose-dependent manner and were not toxic to normal retina glial cells. Both FAAs caused apoptotic cell death through the loss of mitochondrial integrity (ΔΨm), probably by activating cannabinoid receptors, and inhibiting the PI3K/Akt pathway. In conclusion, FAAs derived from natural products may have the potential to treat glioma-type brain cancer.
摘要：
神经胶质瘤是一种以高度侵袭性方式作用于中枢神经系统(CNS)的肿瘤。胶质瘤偶尔会被诊断不准确，治疗效果低，这意味着患者在诊断后存活不到一年。由于肿瘤内细胞变异性等因素，无效的化疗药物，对药物的适应性耐药性发展和切除后肿瘤复发，继续寻找能够抑制神经胶质瘤细胞生长的新药。因此，内源性大麻素类似物，如脂肪酸酰胺(FAA)，代表抑制肿瘤生长的有趣替代品，因为FAA可以调节与癌症相关的几种代谢途径，因此，可能具有治疗胶质母细胞瘤的潜力。本研究的目的是研究两种脂肪乙醇酰胺（FAA1和FAA2）的体外作用，通过直接酰胺化从andiroba油（CarapaguianensisAublet）合成，C6胶质瘤细胞。FAA1和FAA2降低C6细胞活力，增殖和迁移潜力呈剂量依赖性，对正常视网膜胶质细胞没有毒性。两种FAA都通过线粒体完整性的丧失（ΔkWm）引起凋亡细胞死亡，可能是通过激活大麻素受体，并抑制PI3K/Akt途径。总之,源自天然产物的FAA可能具有治疗神经胶质瘤型脑癌的潜力。
