Clitocine, an adenosine nucleoside analog derived from mushrooms, is a potent readthrough. As an inhibitor of nonsense mutations, it can induce the production of p53 protein in cells carrying p53 nonsense mutant alleles. It induces apoptosis in multidrug-resistant tumor cells by targeting Mcl-1. Has anticancer activity.
in vitro
Clitocine incorporation into mRNA is required for premature stop codon readthrough activity, and the presence of clitocine at the third position of a premature stop codon is sufficient to promote robust readthrough. Clitocine (0-0.8 μM ; 24 hours) enhances TRAIL-lethality in in LS411N and SW620 cells. It (0.2μM; 36 hours) significantly potentiates TRAIL-mediated apoptosis.
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in vivo
Citocine (0.3-3 mg/kg; sc; five times per week)-induced p53 inhibits CAOV-33 p53-UAA136 tumor growth in a xenograft model.
