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

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.

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

“…Cancer metastasis is the multistep process of cancer cells spreading from their original site to other distant sites of the body [ 32 – 34 ]. During metastasis, cancer cells in an anchorage-independent condition are likely to die in the process of anoikis, a detachment-induced apoptosis; however, metastatic cells utilize several mechanisms to escape anoikis and consequently grow at distant sites [ 22 , 35 , 36 ]. Among several potentiating factors of metastasis, the transition of epithelial to mesenchymal phenotype, known as EMT [ 6 , 37 , 38 ], has garnered most attention [ 39 – 41 ].…”

“…Anchorage-independent growth was determined by the soft agar colony-formation assay, modified from Phiboonchaiyanan PP. et al’s method [ 22 ]. H460 cells were pre-treated with phoyunnanin E at non-toxic concentrations (0–10 μM) for 48 h at 37 °C.…”

TRIM59 induces epithelial‑to‑mesenchymal transition and promotes migration and invasion by PI3K/AKT signaling pathway in medulloblastoma

“…For instance, it was shown that in ovarian cancer, the activation of EMT is associated with chemoresistance, the latter of which can cause cancer recurrence and metastasis following conventional treatment against ovarian cancer ( 25 , 26 ). Additionally, benzophenone-3 has been demonstrated to increase metastasis potential in lung cancer via the induction of EMT ( 27 ). Following full review of the EMT data in the present study, together with the cell migration and invasion assays, it is concluded that TRIM59 may promote metastasis in medulloblastoma.…”

Chlorination of oxybenzone and prediction of transformation products using non-equilibrium “forced” molecular dynamics

“…Like BPA, OxBZ and related compounds can form mutagenic and genotoxic metabolic byproducts by photo-oxidative stress responses [9] or DNA-adduct formation involving bio-activation by cytochrome P450 enzymes [11,12]. Oxybenzone and other benzophenones also increase tumor metastasis potential by inducing proliferation in cancer cell lines via estrogen-mediated [13,14] and non-estrogenic mechanisms [15].…”