Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Cannabis Cannabinoid Res. 2024 Aug;9(4):e1159-e1169. doi: 10.1089/can.2022.0344. Epub 2023 Mar 21.
Studies have reported that cannabinoids, in particular Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), significantly reduce cancer cell viability . 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. 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. 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 Δ-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. 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 (Δ-THC, CBD, and KM-233) increase when serum is omitted from the media. In addition, dose-response curves for these drugs demonstrated lower IC 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 Δ-THC and CBD to plastic. 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).
研究表明，大麻素，特别是Δ-四氢大麻酚（Δ-THC）和大麻二酚（CBD），可显著降低癌细胞活力。然而，治疗条件在不同的报告中差异很大。特别是，大多数报告采用血清浓度降低（0-3%）的条件，这可能会影响细胞自身的生长以及观察到的结果。本研究旨在验证以下假设：根据其已知的蛋白结合特性，大麻素在胎牛血清（FBS）存在的情况下效果较差。此外，我们希望确定在这些条件下，这些治疗方法是否具有细胞毒性或细胞抑制作用。六种癌细胞系，代表三种不同类型癌症（胶质母细胞瘤、黑色素瘤和结直肠癌[CRC]）的两个独立系，用 10μM 纯Δ-THC、CBD、KM-233 和 HU-331 处理 48 小时（有或没有 FBS）。用 MTT 法测定细胞活力。然后生成剂量-反应曲线，比较相同条件下四种大麻素的效力。我们发现，无血清培养基本身会使 CRC 细胞停滞在细胞周期中，并减缓其他癌症类型的细胞生长。当从培养基中去除血清时，四种大麻素中的三种（Δ-THC、CBD 和 KM-233）的抗肿瘤作用增强。此外，在所有细胞系中，与含有 10%血清的培养基相比，无血清培养基的药物剂量-反应曲线显示出较低的 IC 值。第四种化合物 HU-331 在这两种条件下同样有效。我们观察到的另一个混杂因素是，去除血清会导致 Δ-THC 和 CBD 与塑料强烈结合。在没有 FBS 的情况下治疗癌细胞似乎可以增强大麻素的效力。然而，去除 FBS 本身会损害细胞生长，代表一种不太生理的条件。鉴于大麻素 90-95%与蛋白结合，并且对塑料具有众所周知的亲和力，在细胞不能最佳生长且不能假设已知浓度的情况下（即无 FBS 条件）治疗细胞可能是不明智的。
