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The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells

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Tumor Biology

Abstract

Lung cancer has been the major cause of death within patients due to the high metastatic rate. One of the most essential processes of metastasis is the ability of cancer cells to resist the programmed cell death in a detached condition called anoikis. The discoveries of new natural compound that is able to sensitize anoikis in cancer cells have garnered the most interest in cancer pharmaceutical science. Gigantol, a bibenzyl compound extracted from Dendrobium draconis, has been a promising natural derived compound for cancer therapy due to several cytotoxic effects in cancer cells. This study has demonstrated for the first time that gigantol significantly decreases lung cancer cells’ viability in a detached condition through anoikis and anchorage-independent assays. Western blotting analysis reveals that gigantol greatly decreases epithelial to mesenchymal transition (EMT) markers including N-cadherin, vimentin, and Slug leading to a significant suppression of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and caveolin-1 (cav-1) survival pathways during the detached condition. Therefore, gigantol could be a potential cancer therapeutic compound suggesting for further development for cancer therapy.

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Abbreviations

EMT:

Epithelial to mesenchymal transition

AKT:

Protein kinase B

ERK:

Extracellular signal-regulated kinase

cav-1:

Caveolin-1

ECM:

Extracellular matrix

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Acknowledgments

The authors would like to thank Professor Boonchoo Sritularak for gigantol preparation. This work was supported by the 100th Anniversary Chulalongkorn University fund for doctoral scholarship and the Ratchadapiseksomphot Endowment Fund (2013), Chulalongkorn University (CU-56-384-HR).

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Authors and Affiliations

  1. Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, 10330

    Thitita Unahabhokha

  2. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, 10330

    Pithi Chanvorachote & Varisa Pongrakhananon

  3. Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand, 10330

    Thitita Unahabhokha, Pithi Chanvorachote & Varisa Pongrakhananon

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  1. Thitita Unahabhokha
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  3. Varisa Pongrakhananon
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Correspondence to Varisa Pongrakhananon.

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Unahabhokha, T., Chanvorachote, P. & Pongrakhananon, V. The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells. Tumor Biol. 37, 8633–8641 (2016). https://doi.org/10.1007/s13277-015-4717-z

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  • DOI: https://doi.org/10.1007/s13277-015-4717-z

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