Benzyl isothiocyanate inhibits invasion and induces apoptosis via reducing S100A4 expression and increases PUMA expression in oral squamous cell carcinoma cells

Abstract

Benzyl isothiocyanate (BITC) has been shown to inhibit invasion and induce apoptosis of various types of cancer. However, its role on human oral squamous cell carcinoma (OSCC) cells is still not well elucidated. In the present study, we investigated the effect of BITC on apoptosis and invasion of SCC9 cells, and its underlying mechanisms in vitro and in vivo . SCC9 cells were exposed to BITC (5 and 25 μM) for 24 and 48 h. Cell growth, apoptosis, invasion, and migration were detected in vitro by MTT, FITC-conjugated annexin V/propidium iodide staining followed by flow cytometry, Matrigel-coated semi-permeable modified Boyden, and wound-healing assay. S100A4, PUMA, and MMP-9 expressions were detected to investigate its mechanisms. Xenotransplantation experiments were used to investigate the role of BITC on tumor growth and lung metastasis. BITC inhibited cell viability and induced cell apoptosis in a dose- and time-dependent manner through upregulation of PUMA signals. BITC inhibited cell invasion and migration by downregulation of S100A4 dependent MMP-9 signals. The ip administration of BITC reduced tumor growth but not lung metastasis of SCC9 cells subcutaneously implanted in nude mice. BITC treatment activated pro-apoptotic PUMA and inhibited S100A4-dependent MMP-9 signals, resulting in the inhibition of cell growth and invasion in cultured and xenografted SCC9 cells. Thereby, BITC is a potential therapeutic approach for OSCC.

Nanoparticles induce genetic, biochemical, and ultrastructure variations in Salvadora persica callus

“…Salvadora persica is a reliable natural supply for extracting benzyl isothiocyanate (BITC) that is believed to be promising within the development of anticancer medications. Recently, BITC found to inhibit prostate cancer [11], lung cancer [12], oral cancer [13], and invasion of hepatocellular carcinoma [14].…”

Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes

“…The transcriptome analysis revealed several genes, which are associated with the regulation of cell survival such as S100A4 and SYK, both of which were upregulated in EJ28P. Incidentally, S100A4 expression is positively regulated by the Wnt/β-catenin signalling pathway [ 40 ] to protect cells from pro-apoptotic stimuli [ 41 , 42 ]. It was reported that the knockdown of S100A4 decreased cellular proliferation and promoted apoptosis [ 42 ].…”

Epithelial–Mesenchymal Transition Associated with Head and Neck Squamous Cell Carcinomas: A Review

“…The use of isothiocyanates (ITCs), which are natural compounds found in crucifer vegetables, has been proposed. These ITCs are related to anti-proliferative and apoptotic activity, as they are capable of destabilizing the mitochondrial membrane and inducing apoptosis by the increase in Bax and the inhibition of Bcl-2 and Bcl-XL [ 181 , 182 ]. Ma et al evaluated the activity of Benzyl isothiocyanate and found that this ITC is capable of promoting apoptosis by the induction of caspase-3 and inhibiting the expression of MMP9, which is related to the induction of EMT [ 182 ].…”