Linoleic and linolelaidic acids differentially influence proliferation and apoptosis of molt-4 leukaemia cells

Abstract

The effects of varying concentrations of linoleic acid and its transisomer linolelaidic acid on the proliferation and the ultrastructural morphology of MOLT-4 T-lymphoblastic leukaemia cells were investigated. At 2 and 4 days after exposure to the fatty acids, the cells were counted by flow cytometry and observed by electron microscopy. After 4 days of treatment, linoleic acid was growth stimulatory at concentrations of 200 μM or less, but was markedly inhibitory at 400 μM. In contrast, linolelaidic acid stimulated proliferation at concentrations of 100 and 200 μM, but inhibited cell growth at 400 μM. Cells treated with 400 μM linoleic acid displayed dense accumulations of characteristic lipid globules and glycogen granules, and exhibited ultrastructural evidence of apoptosis including vacuolization, membrane blebbing and chromatin margination at the nuclear periphery. These results support the notion that geometrical isomerism and concentration of polyunsaturated fatty acids influence the proliferative destiny of cancer cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed a previously documented larger alternatively spliced p53 gene transcript in MOLT-4 cells cultured under reduced serum conditions. However, only wild-type p53 transcripts were amplified by RT-PCR of MOLT-4 cells exposed to phytohaemagglutinin, linoleic acid or linolelaidic acid. © 2001 Academic Press.