Nujiangexathone A, a novel compound from Garcinia nujiangensis, suppresses cervical cancer growth by targeting hnRNPK

Abstract

Cervical cancer is among the most frequently diagnosed cancers in females worldwide. Nujiangexathone A (NJXA), a novel compound from Garcinia nujiangensis, has been shown to have anti-cancer potential. In this study, the anti-tumor effects and the underlying mechanisms of NJXA action were investigated. Our results suggested that NJXA induced G0/G1 cell cycle arrest in HeLa and SiHa cells by down-regulating cyclins B1, E1, and A and cyclin-dependent kinases 2, 4 and 6, while selectively restoring p27. Using two-dimensional gel electrophoresis, we showed that NJXA reduced the expression of heterogeneous nuclear ribonucleoprotein K (hnRNPK) by accelerating ubiquitin-proteasome-dependent hnRNPK degradation, which then induced cell cycle arrest through the c-Myc-cyclin/Cdk-Rb-E2F1 pathway. The loss-of-function study showed NJXA induced cell cycle arrest was mediated by down regulation of hnRNPK protein. In vivo results further confirmed the tumor inhibitory effect of NJXA via the down-regulation of hnRNPK, and NJXA induced no apparent toxicity. Our study suggests that NJXA may be a novel anti-cancer drug candidate, especially for treating cancers with abnormally high hnRNPK expression.

Keywords: Cell cycle; Cervical cancer; Garcinia species; Nujiangexathone A; hnRNPK.