Gossypol exerts its cytotoxic effect on HL-60 leukemic cell line via decreasing activity of protein phosphatase 2A and interacting with human telomerase reverse transcriptase activity

Abstract

In this study, we aimed to investigate the potential relationship between gossypol-induced cytotoxicity of human promyelocytic leukemia cell line (HL-60) leukemic cells and intracellular serine/threonine protein phosphatase (PP) dynamics and human telomerase reverse transcriptase (hTERT) activity. Gossypol was found to be cytotoxic in HL-60 cells with the IC₅₀ dose of 4·5 μM. The combination of gossypol and okadaic acid in IC₅₀ doses revealed the increased cytotoxicity in a time-dependent manner. Treatment of cells with gossypol has shown significant decrease in PP2A activity. The expression of the PP2A catalytic subunit was downregulated in gossypol-treated cells with 24 hours' intervals. hTERT mRNA levels were gradually decreased. In conclusion, during gossypol-induced cytotoxicity, intracellular activity and expression of PP2A was decreased as well as the activity of hTERT. The variation of hTERT activity in gossypol-treated HL-60 cells may be the potential reason for the phosphatase interaction during the gossypol treatment of leukemic cells resulting in cellular cytotoxicity.

Keywords:

• GOSSYPOL
• CYTOTOXICITY
• HL-60 CELL LINE
• PROTEIN PHOSPHATASE
• HTERT