title: Autophagy inhibits cell death induced by the anti-cancer drug morusin.
abstract: Autophagy is a cellular process by which damaged organelles and dysfunctional proteins are degraded. Morusin is an anti-cancer drug isolated from the root bark ofMorus alba. Morusin induces apoptosis in human prostate cancer cells by reducing STAT3 activity. In this study, we examined whether morusin induces autophagy and also examined the effects of autophagy on the morusin-induced apoptosis. Morusin induces LC3-II accumulation and ULK1 activation in HeLa cells. In addition, we found that induction of ULK1 Ser317 phosphorylation and reduction of ULK1 Ser757 phosphorylation occurred simultaneously during morusin-induced autophagy. Consistently, morusin induces autophagy by activation of AMPK and inhibition of mTOR activity. Next, we investigated the role of autophagy in morusin-induced apoptosis. Inhibition of autophagy by treating cells with the 3-methyladenine (3-MA) autophagic inhibitor induces high levels of morusin-mediated apoptosis, while treatment of cells with morusin alone induces moderate levels of apoptosis. Cell survival was greatly reduced when cells were treated with morusin and 3-MA. Taken together, morusin induces autophagy, which is an impediment for morusin-induced apoptosis, suggesting combined treatment of morusin with an autophagic inhibitor would increase the efficacy of morusin as an anti-cancer drug.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University Suwon 16419, Republic of Korea.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University Suwon 16419, Republic of Korea.
authors.forename: Wooju
authors.initials: W
authors.lastname: Na
authors.affiliation: Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University Seoul 02447, Republic of Korea.
authors.forename: Minji
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Molecular Biology, Sejong University Seoul 05006, Republic of Korea.
authors.forename: Shin Jung
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee UniversitySeoul 02447, Republic of Korea; KHU-KIST Department of Converging Science & Technology, Kyung Hee UniversitySeoul 02447, Republic of Korea.
authors.forename: Seok-Geun
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University Suwon 16419, Republic of Korea.
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
keywords: AMP-activated protein kinase; Morusin; anti-cancer drug; apoptosis; autophagy