The Role of Ca²⁺ in (-)-Menthol-induced Human Promyelocytic Leukemia HL-60 Cell Death

Abstract

A human promyelocytic leukemia HL-60 cell line was selected to examine the effect of (-)-Menthol on cell death. Based on the results from morphological changes and the percentage of viable cells in HL-60 cells after treatment with various concentrations of (-)-Menthol, it was shown that (-)-Menthol induced cell death through necrosis, not apoptosis. No cell cycle arrest was found in HL-60 cells examined by flow cytometry analysis. Also, the DNA gel electrophoresis method showed that (-)-Menthol did not induce apoptosis in HL-60 cells. However, it was found that (-)-Menthol induced the production of Ca²⁺ in these examined cells, dose-dependently. When HL-60 cells were pretreated with the chelator (BAPTA) of Ca²⁺ for 3 hours before addition of (-)-Menthol to the culture, a decrease of Ca²⁺ production was observed. Under the same conditions, the percentage of viable HL-60 cells was increased. Apparently Ca²⁺ production is associated with the induction of (-)-Menthol-induced cell death.