title: 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.
authors.affiliation: Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences (Building No. 50, 11F), Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Uemura
authors.forename: Saika
authors.initials: S
authors.lastname: Nizam
authors.forename: Md
authors.initials: M
authors.lastname: Khalequzzaman
authors.forename: Nguyen D
authors.initials: ND
authors.lastname: Thang
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Anwarul A
authors.initials: AA
authors.lastname: Akhand
authors.forename: Hossain U
authors.initials: HU
authors.lastname: Shekhar
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D001464:Barium / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D017382:Reactive Oxygen Species; D001464:Barium; D053148:Caspase 3; D001151:Arsenic