title: PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts.
abstract: Esophageal cancer is one of the least studied and deadliest cancers worldwide with a poor prognosis due to limited options for treatment. Chemotherapy agents such as the microtubule-targeting compounds are the mainstay of palliation for advanced esophageal cancer treatment. However, the toxicity and side effects of tubulin-binding agents (TBAs) have promoted the development of novel, more potent but less toxic TBAs. Herein, we identified 2-[4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-5-[(2-methylprop-2-en-1-yl)oxy] phenol (PPMP) as a novel TBA for esophageal cancer treatment. PPMP markedly inhibited tubulin polymerization, and decreased viability and anchorage-independent growth of esophageal cancer cell lines, effects that were accompanied by G2/M arrest and apoptosis. Importantly, we produced patient-derived esophageal cancer xenografts to evaluate the therapeutic effect of PPMP in a setting that best mimics the clinical context in patients with esophageal cancer. Overall, we identified PPMP as a novel microtubule-destabilizing compound and as a new therapeutic agent against esophageal carcinoma.
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.|The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.|The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.|The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.|China-US (Henan) Hormel Cancer Institute, ZhengZhou, Henan, China.
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.|China-US (Henan) Hormel Cancer Institute, ZhengZhou, Henan, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Oi
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Kanamata
authors.initials: K
authors.lastname: Reddy
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.|The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.|The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.|China-US (Henan) Hormel Cancer Institute, ZhengZhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saleem
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.|The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.|China-US (Henan) Hormel Cancer Institute, ZhengZhou, Henan, China.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008875:Middle Aged; D008958:Models, Molecular; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014404:Tubulin; D050257:Tubulin Modulators; C026733:4-propionyloxy-4-phenyl-N-methylpiperidine; D008614:Meperidine
keywords: esophageal cancer; patient-derived tumor xenograft; tubulin-depolymerizing agent