Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition

Phiboonchaiyanan, Preeyaporn Plaimee; Busaranon, Kesarin; Ninsontia, Chuanpit; Chanvorachote, Pithi

doi:10.1007/s10565-016-9368-3

Original Article
Published: 28 October 2016

Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition

Preeyaporn Plaimee Phiboonchaiyanan¹,
Kesarin Busaranon²,
Chuanpit Ninsontia^1,2 &
Pithi Chanvorachote^1,2

Cell Biology and Toxicology volume 33, pages 251–261 (2017)Cite this article

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Abstract

Exposure to compounds with cancer-potentiating effects can contribute to the progression of cancer. Herein we have discovered for the first time that benzophenone-3 (BP-3), a chemical used as sunscreen in various cosmetic products, enhances the ability of lung cancer cells to undergo metastasis. The exposure of the lung cancer cells to BP-3 at non-toxic concentrations significantly increased the number of anoikis resistant cells in a dose-dependent manner. Also, BP-3 increased the growth rate as well as the number of colonies accessed by anchorage-independent growth assay. We found that the underlying mechanisms of such behaviors were the epithelial to mesenchymal transition (EMT) process of cancer cells, and the increase in caveolin-1 (Cav-1) expression. As both mechanistic events mediated anoikis resistance via augmentation of cellular survival signals, our results further revealed that the BP-3 treatment significantly up-regulated extracellular-signal-regulated kinase (ERK). Also, such compounds increased the cellular levels of anti-apoptotic Bcl-2 and Mcl-1 proteins. As the presence of a substantial level of BP-3 in plasma of the consumers has been reported, this finding may facilitate further investigations that lead to better understanding and evidence concerning the safety of use in cancer patients.

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Abbreviations

BP-3:: Benzophenone-3
EMT:: Epithelial to Mesenchymal Transition
Cav-1:: caveolin-1
Akt:: protein kinase B
ERK:: extracellular-signal-regulated kinase
Bcl-2:: B cell leukemia/lymphoma 2
Mcl-1:: myeloid cell leukemia sequence 1
E-Cad:: E-cadherin
N-Cad:: N-cadherin

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Acknowledgments

This research is supported by Grant for International Research Integration: Chula Research Scholar, Ratchadaphiseksomphot Endowment Fund. The authors would like to thanks Ms. Chayanin Kiratipaiboon and Ms. Thitita Unahabhokha. We thank Mr. Keith Kitson and Mr. Christopher Kennedy, a proofreaders.

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Cell-based Drug and Health Products Development Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
Preeyaporn Plaimee Phiboonchaiyanan, Chuanpit Ninsontia & Pithi Chanvorachote
Departments of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
Kesarin Busaranon, Chuanpit Ninsontia & Pithi Chanvorachote

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Preeyaporn Plaimee Phiboonchaiyanan
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Kesarin Busaranon
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Chuanpit Ninsontia
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Pithi Chanvorachote
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Correspondence to Pithi Chanvorachote.

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Preeyaporn Plaimee Phiboonchaiyanan and Kesarin Busaranon Co-first author

Preeyaporn Plaimee Phiboonchaiyanan and Kesarin Busaranon made equal contributions to this article.

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Phiboonchaiyanan, P.P., Busaranon, K., Ninsontia, C. et al. Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition. Cell Biol Toxicol 33, 251–261 (2017). https://doi.org/10.1007/s10565-016-9368-3

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Received: 08 March 2016
Accepted: 19 October 2016
Published: 28 October 2016
Issue Date: June 2017
DOI: https://doi.org/10.1007/s10565-016-9368-3

Keywords

Benzophenone-3 (BP-3)
Lung cancer cells
Metastasis
Anoikis resistance
Epithelial to mesenchymal transition (EMT)