HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells.

Abstract
Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a. A combination of CPT-11 and nutlin-3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT-11 in the absence of nutlin-3a. Enhancement of the growth inhibitory activity of CPT-11 by nutlin-3a suggests a possible new combinatorial MM chemotherapy regimen.
AuthorsBo Han, Hyeon-Cheol Lee-Okada, Momoko Ishimine, Hajime Orita, Keiko Nishikawa, Tetsuya Takagaki, Kazunori Kajino, Takehiko Yokomizo, Okio Hino, Toshiyuki Kobayashi
JournalFEBS open bio (FEBS Open Bio) Vol. 10 Issue 11 Pg. 2375-2387 (11 2020) ISSN: 2211-5463 [Electronic] England
PMID32961616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Chemical References
  • Imidazoles
  • Mutagens
  • Piperazines
  • Tumor Suppressor Protein p53
  • nutlin 3
  • Irinotecan
  • CES2 protein, human
  • Carboxylesterase
Topics
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
  • Carboxylesterase (metabolism)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Imidazoles (pharmacology, therapeutic use)
  • Irinotecan (pharmacology, therapeutic use)
  • Mesothelioma (drug therapy, genetics, pathology)
  • Mutagens (toxicity)
  • Piperazines (pharmacology, therapeutic use)
  • Tumor Suppressor Protein p53 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: