Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2

Li Wang, Yujuan Zhang, Kangdong Liu, Hanyong Chen, Ran Yang, Xiaoli Ma, Hong Gyum Kim, Ann M. Bode, Dong Joon Kim, Zigang Dong

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Carnosol is a phenolic diterpene that is isolated from rosemary, sage, and oregano. It has been reported to possess anti-oxidant, anti-inflammatory, and anti-cancer properties. However, the molecular mechanism of carnosol's activity against gastric cancer has not been investigated. Herein, we report that carnosol is an RSK2 inhibitor that attenuates gastric cancer growth. Carnosol reduced anchorage-dependent and-independent gastric cancer growth by inhibiting the RSKs-CREB signaling pathway. The results of in vitro screening and cell-based assays indicated that carnosol represses RSK2 activity and its downstream signaling. Carnosol increased the G2/M phase and decreased S phase cell cycle and also induced apoptosis through the activation of caspases 9 and 7 and inhibition of Bcl-xL expression. Notably, oral administration of carnosol suppressed patient-derived gastric tumor growth in an in vivo mouse model. Our findings suggest that carnosol is an RSK2 inhibitor that could be useful for treating gastric cancer.

Original languageEnglish (US)
Pages (from-to)34200-34212
Number of pages13
JournalOncotarget
Volume9
Issue number76
DOIs
StatePublished - Sep 1 2018

Keywords

  • Carnosol
  • Gastric cancer
  • Patient-derived tumor xenograft
  • RSK2

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