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

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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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Correspondence to Pithi Chanvorachote.

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The authors declare that there is no conflict of interests regarding the publication of this manuscript.

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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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  • DOI: https://doi.org/10.1007/s10565-016-9368-3

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