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CELLULAR AND MOLECULAR

Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis

School of Chinese Medicine (W.-P.T., C.-T.C., Z.-X.L.) and Department of Biochemistry (C.H.K.C.), The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Arsenic compounds have been traditionally used to treat a variety of ailments, including skin diseases. Our previous study identified the extract of realgar to possess potent antiproliferative action on HaCaT cells. The present study aimed at evaluating whether several inorganic arsenics found in realgar also possess similar antiproliferative properties. The results showed that arsenic trioxide, arsenic pentoxide, and arsenic iodide had significant antiproliferative action on HaCaT cells, with IC₅₀ values at 2.4, 16, and 6.8 µM, respectively. However, these compounds only modestly inhibited the growth of Hs-68 cells, a normal human skin fibroblast cell line, with IC₅₀ values at 43.4, 223, and 89 µM, respectively, conferring a favorable toxicity profile. In mechanistic studies, all three compounds caused DNA fragmentation as demonstrated by gel electrophoresis and the terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling method. Morphologically, nuclear condensation and DNA fragmentation were observed when the cells were exposed to arsenic compounds. Cell cycle analysis with propidium iodide (PI) staining demonstrated the appearance of sub-G₁ peak and cell arrest at the G₁ phase in the presence of these compounds. Quantitative analysis by annexin V-PI staining revealed that the arsenic-induced apoptotic event was dose-dependent. Moreover, the arsenic compounds were able to activate caspase-3 expression when examined by Western blot analysis. Our experimental data unambiguously demonstrated that induction of cellular apoptosis was mainly responsible for the observed antiproliferation brought about by the arsenic compounds on HaCaT keratinocytes, suggesting that these arsenic compounds are putative agents from which psoriasis-treating topical formulae could be developed.

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				Q. Ge-ping, X. Qing-Yu, L. Bing, L. Yong-an, and Z. Ling-Zhen Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia Toxicology and Industrial Health, September 1, 2009; 25(8): 505 - 515. [Abstract] [PDF]