PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts

Yuqiao Sheng, Kangdong Liu, Qiong Wu, Naomi Oi, Hanyong Chen, Kanamata Reddy, Yanan Jiang, Ke Yao, Haitao Li, Wei Li, Yi Zhang, Mohammad Saleem, Wei Ya Ma, Ann M. Bode, Ziming Dong, Zigang Dong

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)30977-30989
Number of pages13
JournalOncotarget
Volume7
Issue number21
DOIs
StatePublished - May 24 2016

Bibliographical note

Funding Information:
This work was supported by The Hormel Foundation and grants from the National Institutes of Health CA166011, CA172454, CA187027, CA196639, R37 CA081064, and from the National Natural Science Foundation of China 81502628.

Keywords

  • Esophageal cancer
  • Patient-derived tumor xenograft
  • Tubulin-depolymerizing agent

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