Differential effect of ascorbic acid and n‐acetyl‐l‐cysteine on arsenic trioxide‐mediated oxidative stress in human leukemia (HL‐60) Cells

Abstract

Arsenic trioxide (ATO) has been recommended for the treatment of refractory cases of acute promyelocytic leukemia (APL). Recent studies in our laboratory indicated that oxidative stress plays a key role in ATO-induced cytotoxicity in human leukemia (HL-60) cells. In the present investigation, we performed the MTT assay and trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) production in HL-60 cells co-exposed to either ascorbic acid (AA) and ATO or to n-acetyl-l-cysteine (NAC) and ATO. The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in MDA levels with increasing doses of AA. In contrary, the addition of NAC to ATO-treated HL-60 cells resulted in a dose dependent decrease of MDA production. From these results, we conclude that the addition of the ascorbic acid to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS) whereas the addition of NAC under the same experimental condition significantly (p<0.05) decreases the level of ROS formation. Based on these direct in vitro findings, our studies provide evidence that AA may extend the therapeutic spectrum of ATO. The co-administration of NAC with ATO shows a potential specificity for tumor cells, indicating it may not enhance the clinical outcome associated with ATO monotherapy in vivo.

Synthesis, spectroscopic study and anticancer activity of a water-soluble Nb(V) peroxo complex

“…Such data are clearly suggestive of the potential of our complex as a more effective and probably safer chemosensitizing agent in leukemiaoriented chemotherapy. Our experimental results, concerning the absence of cytotoxic effect at low doses of ascorbic acid alone (6 μg/mL: 34 μΜ and 60 μg/ mL: 340 μΜ) on HL-60 cells, are supported by previous bibliographic data [61] according to which physiological doses (10-100 μM) of AA have no effect on the viability of HL-60 cells. Similarly, physiological concentrations of ascorbic acid ranging from 0 to 400 μM have no effect on the growth of a gastric cancer cell line [62].…”

Computational classification of mitochondrial shapes reflects stress and redox state

“…Similarly TNF-α (R&D Systems, Minneapolis, MN, USA) was also used for ROS induction, at a concentration of 20 ng/ml. 22 NAC, which is a ROS scavenger (Cayman, Ann Arbor, MI, USA), was used at a concentration of 100 μℳ 23 …”

Malathion‐induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG2) cells

“…All samples were centrifuged at 15,000 rpm for 10 min and 200μl aliquot of the sample was assayed for malondialdehyde (MDA) according to the lipid peroxidation assay kit protocol (Calbiochem-Novabiochem, San Diego, CA). The absorbance of the sample was monitored at 586 nm, and the concentration of MDA was determined from a standard curve (Janero 1990; Yedjou et al, 2008)…”