Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell lines tested (H2052, H2373, H28 and MSTO-211H). Caffeine sensitized H2052 cells in a dose- and schedule-dependent manner, and was associated with a markedly decreased clonogenic survival. Caffeine sensitization occurred only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization was also observed with the clinically better tolerated caffeine analog, theobromine. Pemetrexed sensitization by caffeine was associated with an increase in pemetrexed-induced phosphorylation of ataxia-telangiectasia-mutated (ATM) and Chk1. These data indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based chemotherapy.

Original languageEnglish (US)
Pages (from-to)819-827
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume61
Issue number5
DOIs
StatePublished - Apr 2008

Fingerprint

Pemetrexed
Mesothelioma
Caffeine
Cells
Cell Line
Theobromine
Folic Acid Antagonists
Ataxia Telangiectasia
Phosphorylation
Chemotherapy
Non-Small Cell Lung Carcinoma
Appointments and Schedules

Keywords

  • Caffeine
  • Mesothelioma
  • Pemetrexed
  • Theobromine

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed. / Min, Sang Hee; Goldman, I. David; Zhao, Rongbao.

In: Cancer Chemotherapy and Pharmacology, Vol. 61, No. 5, 04.2008, p. 819-827.

Research output: Contribution to journalArticle

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