Effects of arsenic compounds on growth, cell-cycle distribution and apoptosis of tretinoin-resistant human promyelocytic leukemia cells.

Abstract:

BACKGROUND/AIM:The effects of inorganic and organic arsenicals on proliferation, cell-cycle distribution, and apoptosis of all-transretinoic acid (ATRA)-resistant human promyelocytic leukemia HL-60 (HL-60-R2) cells were herein investigated. MATERIALS AND METHODS:Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell-cycle distribution and apoptotic cells were analyzed by flow cytometry. RESULTS:The 50% inhibitory concentrations (IC50 values) for As2O3 against proliferation of HL-60 and HL-60-R2 cells were 12.2 and 7.2 μM, while those for arsenate were >200 and 62.1 μM, respectively. In contrast, organic methylarsinic acid, dimethylarsonic acid, trimethylarsine oxide, and tetramethylarsonium did not exert any inhibitory effects even at 200 μM. As2O3 and arsenate increased the proportion of apoptotic cells dose-dependently at a concentration range of 5-200 μM. As2O3 did not activate caspase 3/7 in HL-60 and HL-60-R2 cells. CONCLUSION:As2O3 and arsenate inhibit cell proliferation, affect cell-cycle distribution, and induce apoptosis of ATRA-resistant HL-60-R2 cells. The apoptosis-inducing mechanism appears not to be mediated through caspase3/7.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Sakai C,Arai M,Tanaka S,Onda K,Sugiyama K,Hirano T

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

6489-94

issue

11

eissn

0250-7005

issn

1791-7530

pii

34/11/6489

journal_volume

34

pub_type

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