CBN (cannabinol) as anti-tumor agent
About 10% of all extracranial pediatric solid tumors are neuroblastoma. This is a highly heterogeneous form of cancer, accounting for 15% of all cancer-related deaths in children. Fighting it involves understanding numerous genetic, epigenetic, and molecular mechanisms that manage its growth, survival and metastasis. There are germline mutations of anaplastic lymphoma kinase (ALK) and paired-like homeobox 2B (PHOX2B) genes in the mix, and potentially pathogenic germline variants of theCHEK2,PINK1 andBARD1 genes. There are dysregulated histone modifications. And there are signaling pathways too, notably, PI3K/AKT/mTOR, Polo-like kinase 4, which regulates centriole replication, and the hedgehog and NF-κB pathways.
Evidence is accumulating that cannabinoids have some anticancer effects. We have written about this in other blog posts. A study at the Universities of Lethbridge and Calgary, published just this year (Wang B, et al., Cancers (Basel). 2022 Apr 10;14(8):1908. doi: 10.3390/cancers14081908) has shownthat, in two neuroblastoma cell lines IMR-5 (wild-type p53) and SK-N-AS (mutant p53), CBN dose-dependently attenuates cell proliferation, angiogenesis, and invasion, and that it does so by inhibiting the AKT pathway – possibly by affecting CB2 expression – and upregulating miR-34a, which silences E2F1. A 31-nt tRNAiMet fragment (tRiMetF31) deriving from miR-34a-guided cleavage may inhibit cell proliferation by directly targeting PFKFB3. This itself would offer new insight into a miR-34a tumor suppressor network in neuroblastoma.
Until now, the inhibitory effect of CBN on neuroblastoma was unstudied. More study appears warranted. This is encouraging, because in multimodal therapy for juvenile neuroblastoma, serious endocrine and growth side effects have been reported. Novel therapeutic approaches are needed.
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The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.