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

doi:10.18632/oncotarget.9050

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 journal › Article › peer-review

4 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 language	English (US)
Pages (from-to)	30977-30989
Number of pages	13
Journal	Oncotarget
Volume	7
Issue number	21
DOIs	https://doi.org/10.18632/oncotarget.9050
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{a18905fc6ba34dfeba46a672c44b376c,

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.",

keywords = "Esophageal cancer, Patient-derived tumor xenograft, Tubulin-depolymerizing agent",

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

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.",

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doi = "10.18632/oncotarget.9050",

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AU - Sheng, Yuqiao

AU - Liu, Kangdong

AU - Wu, Qiong

AU - Oi, Naomi

AU - Chen, Hanyong

AU - Reddy, Kanamata

AU - Jiang, Yanan

AU - Yao, Ke

AU - Li, Haitao

AU - Li, Wei

AU - Zhang, Yi

AU - Saleem, Mohammad

AU - Ma, Wei Ya

AU - Bode, Ann M.

AU - Dong, Ziming

AU - Dong, Zigang

N1 - 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.

PY - 2016/5/24

Y1 - 2016/5/24

N2 - 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.

AB - 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.

KW - Esophageal cancer

KW - Patient-derived tumor xenograft

KW - Tubulin-depolymerizing agent

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

Abstract

Bibliographical note

Keywords

UN SDGs

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