Artonin E mediates MCL1 down-regulation and sensitizes lung cancer cells to anoikis

Ekkarat Wongpankam, Preedakorn Chunhacha, Varisa Pongrakhananon, Boonchoo Sritularak, Pithi Chanvorachote

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Anoikis, or detachment-induced apoptosis, is recognized as a key inhibitory process of cancer metastasis. Since lung cancer cells possess an ability to resist anoikis, resulting in a high rate of metastasis and death, the present study aimed to investigate the possible anoikis-sensitizing effect of artonin E (AE). Materials and Methods: AE was extracted from bark of Artocarpus gomezianus. Anoikis sensitization of AE was investigated in H460, A549 and H292 human lung cancer cells. The level of anoikis-related proteins was determined by western blot analysis and viable cells were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method. Results: AE was shown to enhance anoikis of H460 cells in a dose-dependent manner. We investigated the underlying mechanisms of AE on anoikis sensitization and found that AE sensitized the cells by down-regulating the anti-apoptotic myeloid leukemia cell sequence-1 (MCL1) protein but had no significant effect on other proteins of the B-cell lymphoma-2 (BCL2) family, including BCL2 and BCL2-associated X protein (BAX). Anoikis sensitization of AE was consistently observed in A549 and H292 lung cancer cells. Conclusion: The present study demonstrates a novel activity of AE on lung cancer cell anoikis for the first time which might lead to the development of a new strategy for lung cancer therapy.

Original languageEnglish (US)
Pages (from-to)5343-5351
Number of pages9
JournalAnticancer Research
Volume32
Issue number12
StatePublished - Dec 1 2012

Keywords

  • A549
  • Anoikis
  • Artonin E
  • H292
  • H460
  • Hk2 cells
  • Lung cancer cells
  • MCL1
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wongpankam, E., Chunhacha, P., Pongrakhananon, V., Sritularak, B., & Chanvorachote, P. (2012). Artonin E mediates MCL1 down-regulation and sensitizes lung cancer cells to anoikis. Anticancer Research, 32(12), 5343-5351.