人类口腔鳞状细胞癌细胞中的 DNA 损伤和细胞死亡:大麻二酚的潜在生物学效应。
DNA damage and cell death in human oral squamous cell carcinoma cells: The potential biological effects of cannabidiol.
发表日期:2024 Oct 16
作者:
Monia Billi, Stefano Pagano, Gian Luca Pancrazi, Chiara Valenti, Stefano Bruscoli, Alessandro Di Michele, Marta Febo, Francesco Grignani, Lorella Marinucci
来源:
Cell Death & Disease
摘要:
本研究检查了大麻二酚 (CBD) 对口腔鳞状细胞癌细胞 (HSC-3) 的体外影响,大麻二酚 (CBD) 是大麻的主要化学成分,被提议作为癌症治疗的新型辅助疗法。细胞活力(MTT 测定) 、形态学 (SEM)、细胞凋亡和细胞周期(流式细胞术)以及 DNA 损伤(磷酸-γ-H2AX 免疫荧光)进行了评估。使用 100μM 和 1μM 之间的浓度评估细胞毒性,并选择两个浓度进行后续分析:25μM,作为有毒剂量,6.25μM,作为无毒剂量。CBD 导致细胞活力呈剂量和时间依赖性降低。 72 小时后,25μM、50μM 和 100μM 分别为 64%、96% 和 99% (p < 0.001),细胞周期停滞在 G0-G1 期,细胞凋亡增加,特别是 25μM 在 72 小时时( p < 0.001),25μM 时出现显着的形态变化,即使在 6.25μM 时仍然存在,考虑到高阳性细胞(5 个磷酸化 γH2AX 焦点)百分比显着增加,细胞损伤显着增加,25μM 时约为 29% 6.25μM 24 小时后为 19%。CBD 抑制口腔癌生长,导致 DNA 损伤。一般来说,诱导的细胞毒性似乎与剂量和时间相关。 CBD 剂量≥25μM 显示活力显着降低。 CBD 可能代表一种新的治疗分子,因为它具有针对口腔鳞状细胞癌的细胞毒性作用。 CBD 产生抑制作用的机制需要进一步研究。版权所有 © 2024 Elsevier Ltd. 保留所有权利。
The present study examined the in vitro effects on oral squamous cell carcinoma cells (HSC-3) of cannabidiol (CBD), the main chemical component of Cannabis, proposed as a novel adjuvant therapy in the treatment of cancers.Cell viability (MTT assay), morphology (SEM), apoptosis and cell cycle (flow cytometry), and DNA damage (phospho-γ-H2AX immunofluorescence) were evaluated. Cytotoxicity was evaluated with concentrations between 100 µM and 1 µM, and two concentrations were selected for subsequent analysis: 25 µM, as toxic dose, and 6.25 µM, as non-toxic.CBD caused a dose- and time-dependent reduction in viability of 64 %, 96 %, and 99 % with 25 µM, 50 µM and 100 µM, respectively, after 72 h (p < 0.001), cell cycle arrest in G0-G1 phase with increased apoptosis in particular at 72 h for 25 µM (p < 0.001), significant morphological alterations with 25 µM, still present even at 6.25 µM, and significantly increased cell damage considering a significant increase in the percentage of highly positive cells (5 phosphorylated γH2AX foci), which is around 29 % for 25 µM and 19 % for 6.25 µM after 24 h.CBD inhibits oral cancer growth causing DNA damage. In general, induced cell cytotoxicity appears to be dose- and time-related. Doses of CBD ≥25 μM showed a high reduction in viability. CBD could possibly represent a new therapeutic molecule for its cytotoxic effects against oral squamous cell carcinoma. The mechanism involved in the suppressive effect caused by CBD needs further investigation.Copyright © 2024 Elsevier Ltd. All rights reserved.