大麻素作为潜在癌症治疗药物的浓度困境。
Cannabinoids as Potential Cancer Therapeutics: The Concentration Conundrum.
发表日期:2023 Mar 21
作者:
Nurgul Carkaci-Salli, Wesley M Raup-Konsavage, Deepkamal Karelia, Dongxiao Sun, Cheng Jiang, Junxuan Lu, Kent E Vrana
来源:
Cellular & Molecular Immunology
摘要:
背景:研究已经报道,特别是 Δ9-四氢大麻酚(Δ9-THC)和大麻二酚(CBD),大麻素可以显著减少体外癌细胞的活力。不幸的是,治疗条件在报告中有很大的差异。特别是,大多数报告使用低清血清浓度(0-3%)的条件,可能会损害细胞自身的生长以及观察到的结果。
目的:本研究旨在测试一个假设,即基于它们已知的蛋白质结合特性,大麻素在胎牛血清(FBS)存在下的效果较差。此外,我们希望确定在这些条件下治疗是否会产生细胞毒性或细胞毒。
方法:用10μM纯Δ9-THC、CBD、KM-233和HU-331处理代表三种不同癌症(胶质母细胞瘤、黑色素瘤和结直肠癌[CRC])的两条独立细胞系的6个癌细胞系,处理时间为48小时(存在或不存在FBS)。采用MTT测定细胞的存活率。然后产生剂量反应曲线,比较四种大麻素在相同条件下的效力。
结果:我们发现仅血清无培养基可以阻止CRC细胞的细胞周期和减缓其他癌症类型的细胞生长。三种大麻素(Δ9-THC、CBD和KM-233)的抗肿瘤效果在介质中不含血清时增加。此外,这些药物的剂量反应曲线表明,在所有细胞系中,无血清培养基与含10%血清的培养基相比,这些药物的IC50值较低。第四种化合物HU-331在两种条件下同样有效。我们观察到的另一个混淆因素是,不含血清会产生Δ9-THC和CBD对塑料的显著结合。
结论:在没有FBS的条件下治疗癌细胞似乎可以增强大麻素的效力。然而,FBS的缺失本身会损害细胞生长,代表一个不太生理的状况。鉴于大麻素90-95%与蛋白质结合并已知对塑料的亲和力,可能不明智在细胞不适当生长且无法假定已知浓度的条件下治疗细胞(即无FBS的条件)。
Background: Studies have reported that cannabinoids, in particular Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), significantly reduce cancer cell viability in vitro. Unfortunately, treatment conditions vary significantly across reports. In particular, a majority of reports utilize conditions with reduced serum concentrations (0-3%) that may compromise the growth of the cells themselves, as well as the observed results. Objectives: This study was designed to test the hypothesis that, based on their known protein binding characteristics, cannabinoids would be less effective in the presence of fetal bovine serum (FBS). Moreover, we wished to determine if the treatments served to be cytotoxic or cytostatic under these conditions. Methods: Six cancer cell lines, representing two independent lines of three different types of cancer (glioblastoma, melanoma, and colorectal cancer [CRC]), were treated with 10 μM pure Δ9-THC, CBD, KM-233, and HU-331 for 48 h (in the presence or absence of FBS). Cell viability was measured with the MTT assay. Dose-response curves were then generated comparing the potencies of the four cannabinoids under the same conditions. Results: We found that serum-free medium alone produces cell cycle arrest for CRC cells and slows cell growth for the other cancer types. The antineoplastic effects of three of the four cannabinoids (Δ9-THC, CBD, and KM-233) increase when serum is omitted from the media. In addition, dose-response curves for these drugs demonstrated lower IC50 values for serum-free media compared with the media with 10% serum in all cell lines. The fourth compound, HU-331, was equally effective under both conditions. A further confound we observed is that omission of serum produces dramatic binding of Δ9-THC and CBD to plastic. Conclusions: Treatment of cancer cells in the absence of FBS appears to enhance the potency of cannabinoids. However, omission of FBS itself compromises cell growth and represents a less physiological condition. Given the knowledge that cannabinoids are 90-95% protein bound and have well-known affinities for plastic, it may be ill-advised to treat cells under conditions where the cells are not growing optimally and where known concentrations cannot be assumed (i.e., FBS-free conditions).