College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Cangnan County Qiushi Innovation Research Institute of Traditional Chinese Medicine, Wenzhou 325800, China.
Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Xihu University School of Medicine, Hangzhou 310006, China.
J Pharm Biomed Anal. 2024 Oct 15;249:116379. doi: 10.1016/j.jpba.2024.116379. Epub 2024 Jul 22.
Cannabis sativa L., with a rich history in Chinese folk medicine, includes hemp strains that offer substantial economic and medical benefits due to their non-addictive properties. Hemp has demonstrated various pharmaceutical activities, including anti-inflammatory, antioxidant, and anti-tumor effects. This study explores the potential of hemp oil extract (HOE) in treating colorectal cancer (CRC). Despite its promise, the specific anticancer mechanisms of HOE have not been well understood. To elucidate these mechanisms, we employed mass spectrometry-based metabolomics and proteomics to investigate the global effects of HOE on CRC cells. Additionally, bioinformatics approaches, including bulk RNA-seq and single-cell RNA-seq, were used to identify gene expression differences and cellular heterogeneity. The results were validated using flow cytometry, western blotting, and immunohistochemistry. Our findings reveal that HOE induces significant alterations in purine metabolism pathways, down-regulates c-MYC, and inhibits the expression of cell cycle-related proteins such as CCND1, CDK4, and CDK6, leading to cell cycle arrest in the G1 phase. This comprehensive analysis demonstrates that HOE effectively blocks the cell cycle in the G1 phase, thereby inhibiting colorectal cancer cell proliferation. These findings provide experimental evidence supporting the potential therapeutic use of hemp in medicine.
大麻(Cannabis sativa L.)在中国民间医学中有着悠久的历史,包括那些因非成瘾性而具有巨大经济和医学价值的工业大麻品种。大麻具有多种药物活性,包括抗炎、抗氧化和抗肿瘤作用。本研究探讨了大麻油提取物(HOE)治疗结直肠癌(CRC)的潜力。尽管前景广阔,但 HOE 治疗 CRC 的具体抗癌机制尚未得到充分理解。为了阐明这些机制,我们采用基于质谱的代谢组学和蛋白质组学方法研究了 HOE 对 CRC 细胞的整体影响。此外,还使用 bulk RNA-seq 和单细胞 RNA-seq 等生物信息学方法来识别基因表达差异和细胞异质性。使用流式细胞术、Western blot 和免疫组织化学对结果进行了验证。我们的研究结果表明,HOE 诱导嘌呤代谢途径发生显著改变,下调 c-MYC,并抑制细胞周期相关蛋白如 CCND1、CDK4 和 CDK6 的表达,导致细胞周期在 G1 期停滞。这项综合分析表明,HOE 能有效阻止细胞周期进入 G1 期,从而抑制结直肠癌细胞增殖。这些发现为大麻在医学中的潜在治疗用途提供了实验证据。