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

Ichiro Yajima, Noriyuki Uemura, Saika Nizam, Md Khalequzzaman, Nguyen D. Thang, Mayuko Y. Kumasaka, Anwarul A. Akhand, Hossain U. Shekhar, Tamie Nakajima, Masashi Kato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Our Weldwork 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 eVects, and we examined the eVect 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-μB 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-μB activity and XIAP expression and decreased JNK activity without aVecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer eVect 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.

Original languageEnglish
Pages (from-to)961-973
Number of pages13
JournalArchives of Toxicology
Volume86
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1
Externally publishedYes

Fingerprint

Arsenic
Cell death
Barium
Cells
Apoptosis
X-Linked Inhibitor of Apoptosis Protein
Epithelial Cells
Water
Reactive Oxygen Species
Caspase 3

Keywords

  • Anticancer eVects
  • Apoptosis
  • Arsenic
  • Barium
  • XIAP

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Yajima, I., Uemura, N., Nizam, S., Khalequzzaman, M., Thang, N. D., Kumasaka, M. Y., ... Kato, M. (2012). Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells. Archives of Toxicology, 86(6), 961-973. https://doi.org/10.1007/s00204-012-0848-9

Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells. / Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D.; Kumasaka, Mayuko Y.; Akhand, Anwarul A.; Shekhar, Hossain U.; Nakajima, Tamie; Kato, Masashi.

In: Archives of Toxicology, Vol. 86, No. 6, 01.06.2012, p. 961-973.

Research output: Contribution to journalArticle

Yajima, I, Uemura, N, Nizam, S, Khalequzzaman, M, Thang, ND, Kumasaka, MY, Akhand, AA, Shekhar, HU, Nakajima, T & Kato, M 2012, 'Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells', Archives of Toxicology, vol. 86, no. 6, pp. 961-973. https://doi.org/10.1007/s00204-012-0848-9
Yajima, Ichiro ; Uemura, Noriyuki ; Nizam, Saika ; Khalequzzaman, Md ; Thang, Nguyen D. ; Kumasaka, Mayuko Y. ; Akhand, Anwarul A. ; Shekhar, Hossain U. ; Nakajima, Tamie ; Kato, Masashi. / Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells. In: Archives of Toxicology. 2012 ; Vol. 86, No. 6. pp. 961-973.
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AU - Kumasaka, Mayuko Y.

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AU - Nakajima, Tamie

AU - Kato, Masashi

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