title: WLIP derived from Lasiosphaera fenzlii Reich exhibits anti-tumor activity and induces cell cycle arrest through PPAR-γ associated pathways.
abstract: White-line-inducing principle (WLIP), a lipodepsipeptide isolated from Lasiosphaera fenzlii Reich., which is one of the puffballs, for the first time, has been reported to exhibit anti-microbial activity. However, there are no reports regarding the anti-tumor effects of WLIP. In this study, we reported the anti-cancer effects of WLIP on K562 cells, and its potential effect on the PPAR-γ activation pathway. The obtained results showed that WLIP exerted strong anti-proliferative effect on K562 cells. Moreover, WLIP was found to increase apoptosis and induce G0/Gl arrest. Modeling results from the Surflex-Dock program suggested that PPAR-γ might be the potential anti-tumor target of WLIP, which was confirmed by the experiments that WLIP increased the activity in luciferase reporter assay and the expression of PPAR-γ in Western blot. Besides, WLIP was able to down-regulate the expression of Bcl-xL, Cyclin-D1 in K562 cells. In summary, our novel observations suggested that WLIP might have a potential implication in cancer prevention and treatment, and also showed for the first time that the anti-tumor effect of WLIP might be mediated through modulation of the PPAR-γ activation pathway.
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Meng
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Su
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Congqin
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Ren
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 15999290001@163.com.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China. Electronic address: zhaoqingchun1967@163.com.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000363:Agaricales; D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C530104:CCND1 protein, human; D047630:Depsipeptides; D055666:Lipopeptides; D047495:PPAR gamma; D051020:bcl-X Protein; C000592484:white-line-inducing principle, Lasiosphaera fenzlii; D019938:Cyclin D1
keywords: Apoptosis; K562 cells; Lasiosphaera fenzlii Reich; Molecular docking; PPAR-γ; White-line-inducing principle