Effects of gamma-linolenic acid and arachidonic acid on cell cycle progression and apoptosis induction in normal and transformed cells

Seegers, J.C.; Kock, Maryna de; Lottering, Mona-Liza; Grobler, C.J.S.; Papendorp, D. H. Van; Shou, Yulin; Habbersett, Robert C.; Lehnert, Bruce E.

doi:10.1016/s0952-3278(97)90570-6

Cited by 38 publications

(17 citation statements)

References 22 publications

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“…Various cell lines are sensitive to AA-induced cytotoxicity, such as renal cells (Zager et al, 1997), neurons (Garrido et al, 2000), fibroblasts (Seegers et al, 1997), lymphoblasts (Seegers et al, 1997) and p4502E1 over-expressing Hep G2 cells (Chen et al, 1997). In retinoblastoma cells, AAinduced cell death was classified as apoptotic according to the morphological changes, phosphatidylserine externalization, chromatin condensation, activation of caspase 3, and PARP and lamin B cleavage (Vento et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Pompéia

Freitas

Kim

et al. 2002

Biology of the Cell

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Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 microM, AA was not toxic; at 10-400 microM, AA induced apoptosis and at concentrations beyond 400 microM, necrosis. The minimum exposure time to trigger cell death was of around 1 h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E2 and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis.

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Section: Discussionmentioning

confidence: 99%

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Pompéia

Freitas

Kim

et al. 2002

Biology of the Cell

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“…Other mechanisms demonstrated include: cell cycle arrest, inhibition of cell proliferation and induction of apoptosis [10,28,29], improvement of gap junction communications and induction of E-cadherin [11,30], and reversion of multidrug resistance [16]. It is possible that several of these mechanisms contribute to the enhanced cytotoxic effects of chemotherapeutic agents seen in this study.…”

Section: Discussionmentioning

confidence: 87%

“…GLA is a naturally occurring PUFA found in high concentration in evening primrose oil. Emulsions or lithium salts of GLA have been shown to be active against pancreatic and other cancer cell lines in vitro [9][10][11][12], in in vivo experiments [8,12] and by direct application to human gliomas in clinical studies [13,14]. The major mechanism of antitumour activity is considered to be a direct growth inhibitory effect due to increased membrane lipid peroxidation and free radical damage [15].…”

Section: Introductionmentioning

confidence: 99%

Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines

et al. 2003

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“…Interestingly, in this model, EPA caused a higher rate of TBARS production along with a greater inhibition of tumour growth in vivo than the more unsaturated DHA. Both GLA and AA inhibited the cell cycle in various other tumour cells causing reductions in S-phase and induction of apoptosis [71][72][73]. DHA has also been reported to exert similar effects in leukaemia cells with S-phase cycle arrest, increased p21 expression and increased pro-caspase-3 cleavage leading to increased apoptotic rate [74,75].…”

Section: Fatty Acid Induction Of Cell Deathmentioning

confidence: 92%

Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

Colquhoun

2010

Mol Neurobiol

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Polyunsaturated fatty acids (PUFAs) are known to inhibit cell proliferation of many tumour types both in vitro and in vivo. Their capacity to interfere with cell proliferation has been linked to their induction of reactive oxygen species (ROS) production in tumour tissues leading to cell death through apoptosis. However, the exact mechanisms of action of PUFAs are far from clear, particularly in brain tumours. The loss of bound hexokinase from the mitochondrial voltage-dependent anion channel has been directly related to loss of protection from apoptosis, and PUFAs can induce this loss of bound hexokinase in tumour cells. Tumour cells overexpressing Akt activity, including gliomas, are sensitised to ROS damage by the Akt protein and may be good targets for chemotherapeutic agents, which produce ROS, such as PUFAs. Cardiolipin peroxidation may be an initial event in the release of cytochrome c from the mitochondria, and enriching cardiolipin with PUFA acyl chains may lead to increased peroxidation and therefore an increase in apoptosis. A better understanding of the metabolism of fatty acids and eicosanoids in primary brain tumours such as gliomas and their influence on energy balance will be fundamental to the possible targeting of mitochondria in tumour treatment.

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Effects of gamma-linolenic acid and arachidonic acid on cell cycle progression and apoptosis induction in normal and transformed cells

Cited by 38 publications

References 22 publications

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines

Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

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