title: Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.
abstract: 1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis.
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: He
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: He
authors.affiliation: Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jun
authors.affiliation: Division of Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Manli
authors.initials: M
authors.lastname: Chuai
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Kenneth Ka Ho
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wanglijing62@163.com.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D005910:Glioma / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012074:Remission Induction; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015017:Yolk Sac / Q000098:blood supply / Q000187:drug effects
chemical_list: D004246:Dimethylphenylpiperazinium Iodide
keywords: Angiogenesis; Blood islands; CAM; DMPP; Vasculogenesis; YSM