The natural alkaloid nitidine chloride targets RNA polymerase I to inhibit ribosome biogenesis and repress cancer cell growth.

ABSTRACT: Nature is an abundant and largely untapped source of potent bioactive molecules. Ribosome biogenesis modulators have proven effective in suppressing cancer cell growth and are currently being evaluated in clinical trials for anticancer therapies. In this study, we characterized the alkaloid nitidine chloride (NC), produced by the endemic Cameroonian plant Fagara (and other plants). We demonstrate that NC kills cancer cells regardless of their p53 status and inhibits tumor growth in vitro. Furthermore, NC profoundly suppresses global protein synthesis. Treatment of human cells with NC causes severe nucleolar disruption and inhibits pre-rRNA synthesis by destabilizing key factors required for recruitment of RNA polymerase I to ribosomal DNA promoters. In vitro, NC intercalates into DNA and i

SUBMITTER: Voukeng I 

PROVIDER: S-EPMC11929923 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature