The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents

Abstract

Chemotherapy agents initiate tumour cell apoptosis and this is thought to involve oxidative stress. In this study we have investigated the effect of the important antioxidant Vitamin C (ascorbate) on the response of HL60 and Jurkat cells to three chemotherapy drugs, namely etoposide, melphalan and arsenic trioxide (As(2)O(3)). Cells grown in routine culture media are deficient in ascorbate and to determine its effect on chemotherapy drug-induced apoptosis we supplemented the cells prior to drug exposure. We found that ascorbate had a varied effect on apoptosis and cell cycle progression. Etoposide-induced apoptosis in HL60 cells was significantly increased in ascorbate-loaded cells as measured by caspase-3 activation and DNA degradation, and this appeared to reflect a decrease in the number of necrotic cells rather than increased cytotoxicity. In contrast, ascorbate had no effect on etoposide-induced apoptosis in Jurkat cells. In both cell types melphalan-induced apoptosis was unaffected by intracellular ascorbate, whereas both apoptosis and growth arrest with low concentrations of As(2)O(3) were diminished. These results indicate that intracellular ascorbate can affect cell responses to chemotherapy drugs in a complex and somewhat unpredictable manner and that it may play an important role in the responsiveness of tumour cells to chemotherapy regimes.

Effect of Dimethyl Sulfides on the Induction of Apoptosis in Human Leukemia Jurkat Cells and HL-60 Cells

“…This difference may result in the fundamental difference in the metabolism of Me 2 S 4 , which was involved in radical reactions with the myeloperoxidase, an enzyme that is abundant in HL-60 cells. 26) Taken together, our observations indicate that Me 2 S 3 and Me 2 S 4 induced the generation of reactive oxygen species, and that subsequent caspase-3 activation initiated apoptosis in Jurkat and HL-60 cells. Factors other than the GSH content may have been involved in determining the cell damage such as an alteration in the membrane phospholipids.…”

Ascorbic acid inhibits TPA-induced HL-60 cell differentiation by decreasing cellular H2O2 and ERK phosphorylation

“…High-dose ascorbic acid inhibits HL-60 cell growth, whereas a low-dose does not. Previous studies have demonstrated that a high-dose of ascorbic acid can increase radiation-induced and etoposide-induced apoptosis in HL-60 cells (28,29). Similar to these studies, the present study demonstrated that a high-dose (5 µM) of ascorbic acid inhibited cell growth in the HL-60 cells, whereas a low-dose (5 µM) had no affect on the growth of the HL-60 cells (Fig.…”

“…Previous studies have demonstrated that ascorbic acid can activate the ERK signaling pathway to induce progenitor cell differentiation (26,27). Additionally, several studies have demonstrated that high-doses of ascorbic acid (>100 µM) can activate a caspase cascade to promote radiation-induced and etoposide-induced apoptosis in HL-60 cells (28,29). A previous study also demonstrated that high-doses of ascorbic can induce HL-60 cell apoptosis and induce a fraction of HL-60 cells to express the granulocyte marker, CD 66b (30).…”

Induction of Apoptosis by β-Carotene and Dimethyl Tetrasulfide Assisted by UVA Irradiation in HL-60 Cells

“…10) This difference may originate from a fundamental difference in the metabolism of -carotene assisted by UVA irradiation, which involves radical reactions with myeloperoxidase, an enzyme that is abundant in HL-60 cells. 19) Without UVA irradiation, co-treatment withcarotene significantly enhanced the caspase-3 activity (Fig. 6B), even though it had no significant effect on the cell viability and intracellular ROS level induced by Me 2 S 4 (Figs.…”