Abstract 5269: Cryptotanshinone activate Nrf2 expression through microRNA regulations

Abstract

Abstract Cryptotanshinone is a diterpene quinone derived from the roots of Salvia miltiorrhiza Bunge. An increasing number of studies have demonstrated that cryptotanshinone has the pharmacological activities such as anti-oxidative stress, anti-bacteria, anti-inflammation, and anti-cancer. Cryptotanshinone has been found to increase the ARE expression level induced by the Nrf2 and decrease Keap1 expression. This study investigated Nrf2 and Keap1-related microRNA to understand the mechanisms of cryptotanshinone in antioxidant activities. HepG2 cells were treated with cryptotanshinone 2.5 μM in DMEM medium with 1% FBS for 5 days. Total RNA was obtained for small RNA sequencing and real-time PCR analyses. The analyses revealed that Cryptotanshinone had the potential to inhibit miR-27a-5p, miR-142-5p, miR-28 and miR-93-5p levels, which subsequently increased the Nrf2 mRNA level. On the other hand, the Keap1 mRNA level was suppressed through up-regulation of miR-23a and down-regulation of miR-7-5p. Moreover, Nrf2 and its related downstream anti-oxidant enzymes such as NQO1 and UGT were increased and the Keap1 protein level was decreased. These findings suggest that cryptotanshinone possesses the cancer chemoprevention activity in up-regulation of Nrf2 mRNA and protein levels through the suppression of inhibitory microRNA. Future investigations that extend the current study can focus on pharmacological mechanism of cryptotanshinone as a cancer chemoprevention agent, and the safety of long-term uptake of cryptotanshinone for cancer prevention. Citation Format: Rachmad A. Dongoran, Tien-Yuan Wu. Cryptotanshinone activate Nrf2 expression through microRNA regulations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5269. doi:10.1158/1538-7445.AM2017-5269