EFFECT OF BENZOPHENONE-3 AND MOSCATILIN ON METASTASIS IN HUMAN NON-SMALL CELL LUNG CANCER CELLS

Abstract

Exposure to compounds with cancer-potentiating effect 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 number of colony 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 cell, and the increase in caveolin-1 expression. As both mechanistic events have been shown to mediate 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 compound increased the cellular levels of anti-apoptotic Bcl-2 and Mcl-1 proteins. As the presence of substantial level of BP-3 in plasma of the consumers has been reported, this finding may facilitate the further investigations which lead to the better understandings and evidences concerning the safety of use in cancer patients. Interestingly, a natural compound extracting from traditional orchids called moscatilin was previously reported with promising effects for cancer therapy including anti-proliferation and anti-migration properties. This study also found that moscatilin had the ability to attenuate metastasis process by suppressing the activity of Akt, ERK, and Mcl-1 resulting in a resistance in anoikis process. This study also found that moscatilin had the ability to attenuate metastasis process targeting the above-mentioned anoikis resistance pathways. This finding may indeed facilitate the development of moscatilin for the treatment of cancer.