Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells

Abstract

Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

Effects of ricin extracted from seeds of the castor bean (ricinuscommunis) on cytotoxicity and tumorigenesis of melanoma cells

“…Statistical analysis in this study was performed according to the method described in the previous report (Yajima et al, 2012). Results from three independent experiments in each group were statistically analyzed by Student's t-test.…”

“…A crystal violet assay was performed by the method described in the previous report (Yajima et al, 2012)to primarily assess the viability of cells. Briefly, 3x10 4 cells were plated in six-well plates and cultured in the medium with or without ricin for 48hrs.…”

Treatment of Vemurafenib-Resistant SKMEL-28 Melanoma Cells with Paclitaxel

“…Statistical analysis in this study was performed according to the method described by Yajima (2012). Results from three independent experiments in each group were statistically analyzed by Student's t-test.…”

“…A crystal violet assay was performed by the method described by Yajima (2012) to primarily assess the viability of cells. Briefly, 3x10 4 cells were plated in sixwell plates and cultured in the medium with or without vemurafenib for 72 hrs.…”

Arsenic: an ancient toxicant of continuous public health impact, from Iceman Ötzi until now

“…In the present issue of Archives of Toxicology, Yajima et al (2012) address apoptotic mechanisms induced by co-exposure with barium, which can additionally be present, at concentrations [150 lg/L, in As-containing ([200 lg/L) drinking-water wells in Bangladesh. Two other publications in this issue address co-exposures of arsenic and fluoride.…”