A unique RNA-directed nucleoside analog is cytotoxic to breast cancer cells and depletes cyclin E levels.

摘要: In contrast to deoxyribose or arabinose containing nucleoside analogs that are currently established for cancer therapeutics, 8-chloro-adenosine (8-Cl-Ado) possesses a ribose sugar. This unique analog is RNA-directed and in phase I clinical trial hematological malignancies. therapies effective the treatment of many malignancies as their activities primarily aimed at short-lived transcripts, which typically encoded by genes promote growth survival tumor cells such cyclin E breast cancer. Based on this, we hypothesized 8-Cl-Ado, transcription inhibitor, will be cells. The metabolism 8-Cl-Ado effect ATP cell lines MCF-7 BT-474 were measured using HPLC analysis. these cells, was effectively taken up, converted its cytotoxic metabolite, 8-Cl-ATP, depleted endogenous levels. turn led an inhibition RNA synthesis. synthesis associated with depletion expression, indicative diminished tumorigenic phenotype. final outcome due induction apoptosis loss clonogenic survival. These results indicate clinic malignancies, may agent