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

The effects of varying concentrations of linoleic acid and its transisomer linolelaidic acid on the proliferation 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 microM or less, but was markedly inhibitory at 400 microM. In contrast, linolelaidic acid stimulated proliferation at concentrations of 100 and 200 microM, but inhibited cell growth at 400 microM. Cells treated with 400 microM 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.

Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate.

In previous studies we observed that some allyl sulfides can cause increased acetylation of histones and differentiation in DS19 mouse erythroleukemia cells. In the present work we observed increased acetylation of histones with allyl isothiocyanate and butanethiol but not with butyl sulfide or butyl disulfide. Increased acetylation of histones was established by change in electrophoretic mobility, incorporation of [3H]acetate or immunoblotting. Histone deacetylase in nuclei of DS19 cells was inhibited 74% by 0.5 mM allyl mercaptan and 43% by 0.5 mM butanethiol but was not significantly affected by 0.5 mM allyl isothiocyanate. There was some degree of reversibility in the effect of allyl isothiocyanate when the cells were incubated for 15 hr in fresh medium. The data suggested that allyl isothiocyanate may stimulate histone acetylation rather than inhibit histone deacetylation. Addition of allyl isothiocyanate, however, had very little or no additional effect on the induction of histone acetylation caused by trichostatin A. Histone acetyltransferase activity determined in cell homogenates was not increased by preincubation of cells with allyl isothiocyanate or inclusion of allyl isothiocyanate in the assay medium. It was concluded that treatment of mouse erythroleukemia cells with allyl isothiocyanate can cause increased acetylation of histones but the mechanism for this effect requires further elucidation.

Effects of C18 fatty acid isomers on DNA synthesis in hepatoma and breast cancer cells.

The influence of geometrical isomerism on the growth regulatory effects of 18 carbon unsaturated fatty acids on the incorporation of [3H]thymidine into DNA was studied in 7800NJ rat hepatoma and T47D human breast cancer cells. 9 cis, 12 cis linoleic acid was more inhibitory than the trans 9, trans 12 isomer (linolelaidic acid). The monounsaturated cis isomer, oleic acid, was also more inhibitory than the trans isomer. In contrast to published studies on the proliferation of breast cancer cells, we observed conditions in which linoleic acid was more inhibitory than conjugated linoleic acid for thymidine incorporation into DNA. Increasing the concentration of bovine serum albumin from 1 mg/ml to a physiological concentration of 38 mg/ml greatly diminished inhibitory effects and favored stimulatory effects on hepatoma and breast cancer cells. The results suggested that the growth inhibitory and stimulatory effects of C18 unsaturated fatty acids on cancer cells are influenced by geometrical isomerism and the ratio of the albumin to fatty acid concentrations.