title: Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation.
abstract: Isoliensinine, liensinine and neferine are major bisbenzylisoquinoline alkaloids in the seed embryo of lotus (Nelumbo nucifera), and exhibit potential anti-cancer activity. Here, we explored the effects of these alkaloids on triple-negative breast cancer cells and found that among the three alkaloids isoliensinine possesses the most potent cytotoxic effect, primarily by inducing apoptosis. Interestingly, isoliensinine showed a much lower cytotoxicity against MCF-10A, a normal human breast epithelial cell line. Further studies showed that isoliensinine could significantly increase the production of reactive oxygen species (ROS) in triple-negative breast cancer cells, but not in MCF-10A cells. The isoliensinine-induced apoptosis could be attenuated by radical oxygen scavenger N-acetyl cysteine, suggesting that the cytotoxic effect of isoliensinine on cancer cells is at least partially achieved by inducing oxidative stress. We found that both p38 MAPK and JNK signaling pathways were activated by isoliensinine treatment and contributed to the induction of apoptosis. Furthermore, inhibitors or specific siRNAs of p38 MAPK and JNK could attenuate apoptosis induced by isoliensinine. However, only the p38 inhibitor or p38-specific siRNA blocked the elevation of ROS in isoliensinine-treated cells. Our findings thus revealed a novel antitumor effect of isoliensinine on breast cancer cells and may have therapeutic implications.
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Boxuan
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061986:MCF-7 Cells; D010636:Phenols / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D044182:Benzylisoquinolines; D007546:Isoquinolines; D010636:Phenols; D017382:Reactive Oxygen Species; C499779:isoliensinine; C057222:neferine; C080095:liensinine; D048051:p38 Mitogen-Activated Protein Kinases