Down-regulation of four arsenic antagonists on apoptosis and telomerase activity induced by arsenic trioxide in three myelocytic leukemia cell lines

AIM: To investigate regulative effects of thiol reagents, N-acetyl-l-cystei ne (NAC) and natrii dimercaptosussinas (NDMS), catalase (CAT), and calcium chelator 2-[(2-bis-[carboxymethyl]-amino-5-methyl-phenoxy)-methyl]-6-methox y-8-bis-[carboxy-methyl]-aminoquinoline (Quin 2) on apoptosis and telomeras e activity induced by arsenic trioxide (As2O3) in three myelocytic leukemia cell lines. METHODS: Flow cytometry was used to examine apoptosis and a PC R ELISA kit was used to detect telomerase activity. RESULTS: As2O3 induced about 40 % - 60% of apoptosis in NB4, K562, and HL-60 cells at the concentr ation of 0.6, 2.7, and 8.1 mu mol/L respectively, as well as down-regulated telomerase activities in three cell lines. NAC 4 mmol/L, NDMS 200 mu mol/L , CAT 80 kU/L, and Quin 2 20 mu mol/L could down-regulate apoptosis various ly induced by As2O3. NAC and CAT alone could decline telomerase activity in three cell lines and further decline telomerase activities that had been d ecreased by As2O3, whereas Quin 2 antagonized the decline in K562 and HL-60 cells. CONCLUSION: Thiol activity loss, free radical alteration, intracell ular calcium changes, and decline of telomerase activity might be involved in As2O3-induced apoptosis. NAC, NDMS, CAT, and Quin 2 antagonized in some extent the effect of As2O3 on the three tested cell lines.