大麻提取物、植物大麻素及其乙酰化衍生物对 SHSY-5Y 神经母细胞瘤细胞活力和半胱天冬酶 3/7 激活的影响。
Effect of Cannabis sativa L. extracts, phytocannabinoids and their acetylated derivates on the SHSY-5Y neuroblastoma cells' viability and caspases 3/7 activation.
发表日期:2024 May 27
作者:
Elizabeth Tapia-Tapia, Pablo Aránguiz, Rodrigo Diaz, Luis Espinoza, Caroline R Weinstein-Oppenheimer, Mauricio Cuellar
来源:
Cellular & Molecular Immunology
摘要:
尽管出现了新的生物和免疫疗法,但仍需要针对神经母细胞瘤的新疗法,因为难治性小儿神经母细胞瘤仍然是一个医学挑战。植物大麻素及其半合成衍生物已显示出支持其抗癌潜力的证据。本研究的目的是检查植物大麻素或半合成大麻素,它们会降低 SHSY-5Y(神经母细胞瘤细胞系)的活力。以大麻 L. 为原料,生产己烷和乙酰乙酸酯提取物,然后生产 9-四氢大麻酚(其酸)对应物和 CBN 被分离。此外,还合成了THC和CBN的乙酰化衍生物。通过高效液相色谱法和 1H y 13C 核磁共振测定化学物质的鉴定和纯度。然后,使用刃天青方法检查了影响神经母细胞瘤细胞系 SHSY-5Y 活力的能力。最后,为了深入了解提取物、植物大麻素和乙酰化衍生物对所检查细胞的作用机制,对暴露于这些化合物的细胞进行了 caspase 3/7 测定。证明了分离化合物的结构和纯度。提取物、植物大麻素及其乙酰化对应物抑制 SHSY 5Y 细胞的活力,CBN 是所有测试分子中最有效的,其抑制浓度为 9.5 µM 的 50%。每个评估的分子都表现出激活半胱天冬酶的能力3/7,表明至少部分地,所测试的植物大麻素及其半合成衍生物的细胞毒性是由细胞凋亡介导的。© 2024。作者。
There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability.Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds.The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM.Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.© 2024. The Author(s).