title: Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.
abstract: Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Ministry of Education Key Laboratory of Experimental Teratology and Department of Molecular Medicine and Genetics, Shandong University, Jinan, Shandong, China.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Yinuo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hospital Information Center, People's Hospital of Rizhao, Rizhao, Shandong, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Jieyin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pathology, Northwestern University School of Medicine, Chicago, IL, USA.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Ministry of Education Key Laboratory of Experimental Teratology and Department of Molecular Medicine and Genetics, Shandong University, Jinan, Shandong, China.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China. liujian9782@sdu.edu.cn.|Ministry of Education Key Laboratory of Experimental Teratology and Department of Molecular Medicine and Genetics, Shandong University, Jinan, Shandong, China. liujian9782@sdu.edu.cn.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D031653:Nelumbo / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D010936:Plant Extracts; C057222:neferine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; JNK; Neferine; Ovarian cancer; p38 MAPK