Antiproliferative and anti-invasive effects of inorganic and organic arsenic compounds on human and murine melanoma cells in vitro

作者：Hiwatashi Yoko; Tadokoro Hiroko; Henmi Kayo; Arai Mariko; Kaise Toshikazu; Tanaka Sachiko; Hirano Toshihiko^*

来源：Journal of Pharmacy and Pharmacology, 2011, 63(9): 1202-1210.

DOI：10.1111/j.2042-7158.2011.01330.x

• arsenic compounds
• cell invasion
• collagen matrix
• matrix metalloproteinase
• melanoma cells

Objectives For patients with advanced melanoma, no treatment options are available at present that provide either sufficient response rates or a significant prolongation of overall survival. The present study examines the effects of two inorganic and six organic arsenic compounds on cell proliferation and cell invasion of melanoma cells in vitro.
Methods The effects of arsenic compounds on proliferation of human melanoma A375 cells and murine melanoma B16F10 cells were examined by MTT assay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the effects of the compounds on cell invasion were examined by the Boyden chamber invasion assay. The amounts of active matrix metalloproteinase (MMP)-2 and pro-MMP-2 in the culture supernatant of A375 cells were determined by an MMP-2 activity assay system.
Key findings Arsenate and arsenic trioxide (As2O3) inhibited the proliferation of A375 and B16F10 cells significantly at concentration ranges of 0.1-20 mu g/ml (P < 0.001), while the organic compounds arsenobetaine, arsenocholine, dimethylarsinic acid, methylarsonic acid, tetramethylarsonium and trimethylarsine oxide did not show any inhibitory effects even at 20 mu g/ml. Cell invasion of A375 and B16F10 cells through a layer of collagen IV was significantly inhibited by 0.1-20 mu g/ml of arsenate or As2O3 (P < 0.05), while the organic compounds did not inhibit cell invasion. Arsenate or As2O3 at 0.2-10 mu g/ml significantly inhibited the amount of active MMP-2 and pro-MMP-2 secreted into the A375 cell culture supernatant (P < 0.05).
Conclusions Our findings show that the inorganic arsenic compounds arsenate and As2O3 inhibit cell proliferation and prevent the invasive properties of melanoma cells, possibly by decreasing MMP-2 production from the cells.

• 出版日期2011-9