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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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