Tylophorine compounds exert anti‐cancer activity by targeting a ribonucleoprotein complex containing caprin‐1 and c‐Myc mRNA

Abstract

Tylophorine and its derivatives exhibit anti‐cancer activities, but their cellular targets remain to be elucidated. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine targets and sequesters caprin‐1, G3BP1, c‐Myc mRNA and cyclin D1/D2 mRNA‐associated ribonucleoprotein complexes to the polysomal fractions, thereby repressing the protein expression of the associated mRNA‐transcripts. Gene expression profiling and gain‐of‐c‐Myc‐function experiments in tylophorine‐treated carcinoma cells revealed that the down‐regulation of c‐Myc contributes to the anti‐oncogenic effects of tylophorine. Furthermore, the potent tylophorine derivative dibenzoquinoline‐33b elicited a similar effect, as c‐Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline‐33b.Thus, tylophorine compounds exert anti‐cancer activity predominantly by targeting and sequestering the caprin‐1 protein and c‐Myc mRNA associated ribonucleoprotein complex.(This work was funded by the National Science Council of Taiwan [NSC 102‐2628‐B‐400‐002‐MY3], the National Health Research Institutes, Taiwan, R.O.C., and the Ministry of Economic Affairs, R.O.C. “102‐EC‐17‐A‐02‐04‐1099” & “103‐EC‐17‐A‐22‐1099”.)