Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2
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Li Wang1, Yujuan Zhang1, Kangdong Liu1,2,3,4, Hanyong Chen5, Ran Yang1, Xiaoli Ma1,2, Hong-Gyum Kim1, Ann M. Bode5, Dong Joon Kim1 and Zigang Dong1,5
1China–US (Henan) Hormel Cancer Institute, Henan, China
2The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
3The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan, China
4The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China
5The Hormel Institute, University of Minnesota, Austin, MN, USA
Dong Joon Kim, email: [email protected]
Zigang Dong, email: [email protected]
Keywords: carnosol; RSK2; gastric cancer; patient-derived tumor xenograft
Received: September 22, 2017 Accepted: January 09, 2018 Epub: February 06, 2018 Published: September 28, 2018
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.
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