Ethanol extract of Remotiflori radix induces endoplasmic reticulum stress-mediated cell death through AMPK/mTOR signaling in human prostate cancer cells

Abstract

Remotiflori radix is the root of Mosidae, which has long been used as a traditional medicine to treat chills, fever, and phlegm discharge. The ethanol extract of Mosidae leaves (MLE) possesses strong antioxidant and chemopreventive activities. However, the anti-cancer effects of the Remotiflori radix have not been examined. We used the ethanol extract of Remotiflori radix (ERR) and the PC-3 and DU145 prostate cancer cell lines in this study. We found that > 100μg/mL ERR caused dose- and time-dependent cell death. Autophagic and apoptotic cell numbers increased in a dose-dependent manner as incubation time was prolonged, and LC3 punctuation, YO-PRO-1 uptake, DNA fragmentation, activation of caspases, and PARP cleavage were induced. Phosphorylation of AMPK, ULK, and p38 was increased after ERR treatment, and the level of the ER stress marker CHOP was also elevated. AMPK knockdown dramatically blocked ERR-mediated CHOP expression and cell death, suggesting that AMPK activation and ER stress play a critical role in ERR-induced cell death. Furthermore, oral administration of ERR at 50 mg/kg efficiently suppressed tumorigenic growth of PC-3 cells with no adverse effects. These results suggest that the ERR can be used as a safe and potent alternative therapy for patients with prostate cancer.