California Pacific Medical Center, Research Institute, San Francisco, California, USA.
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Cannabis Cannabinoid Res. 2021 Apr 15;6(2):148-155. doi: 10.1089/can.2019.0081. eCollection 2021 Apr.
We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 () in cancer cells, leading to inhibition of tumor progression . While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate. We confirmed that was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation. Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.
我们之前报道过,大麻二酚(CBD)是一种具有低毒性特征的大麻素,可下调促转移基因抑制剂 DNA 结合蛋白 1()在癌细胞中的表达,从而抑制肿瘤进展。虽然 CBD 被广泛使用,包括癌症患者的自我用药,并且 CBD 为基础的疗法正在进行癌症治疗的临床评估,但它的作用机制仍知之甚少。在这项研究中,我们使用微阵列分析和 Western blot 分析进行验证,试图确定 CBD 在各种侵袭性癌细胞系中调节的全基因组谱,包括乳腺、脑、头颈部和前列腺。我们证实是 CBD 下调的主要靶点,还发现 CBD 抑制了叉头框转录因子 M1(FOXM1),它是一种参与细胞增殖的转录激活因子,同时上调了生长分化因子 15(GDF15),一种与组织分化相关的细胞因子。我们的结果表明,通过调节共同的关键致癌基因的表达,CBD 可能代表一种有前途的非毒性治疗方法,用于治疗各种来源的肿瘤。