The decreased transfer of arachidonic acid from triglycerides to phospholipids during proliferation of a human gastric tumor (HGT) cell line is not linked to modification of membrane fluidity

Najid, A; Es-Saady, D.; Denizot, Yves

doi:10.1016/0304-3835(94)90259-3

Cited by 4 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The difficulties of simulating the physiological ECM and of maintaining viability for normal cells in culture have been noted [47]. These considerations suggest the hypothesis that fluidization of the plasma membrane caused by UFAs [21,48,49] is a key event triggering ultimate tumor cell death, as has been proposed [50,51]. …”

Section: Discussionmentioning

confidence: 99%

“…Supplementation by ALA or oleic acid, in particular, caused fluidization and destabilization in model membranes, an effect related to the hook and boomerang shapes, respectively, of these molecules [65]. Sharp peaks of membrane fluidization were observed in cultured human cancer cell membranes 3 days after exposure to ALA [21] and to linoleic acid [49] with a less pronounced peak for oleic acid at 2-4 days [49]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: concentration thresholds and implications for clinical efficacy

Scheim¹

2009

Lipids Health Dis

View full text Add to dashboard Cite

BackgroundUnsaturated fatty acids (UFAs) exhibit in vitro cytotoxicity against many malignant cell lines and yield decreased cancer incidence and reduced tumor growth in animal models. But clinical and animal studies to date have achieved response using only localized delivery methods such as intratumoral infusion. To explore possibilities for enhanced clinical efficacy, fresh surgical explants of tumors from 22 patients with five malignancies were exposed to γ-linolenic acid (GLA) and α-linolenic acid (ALA) and analyzed with an in vitro chemosensitivity testing system, the Fluorescent Cytoprint Assay (FCA). A total of 282 micro-organ cultures derived from these malignant tumors were exposed to GLA and ALA at different concentrations.ResultsGLA and ALA exhibited greater than 90% cytotoxicity at a sharp concentration threshold between 500 μM and 1 mM against all but two malignant micro-organ cultures tested in 5-10% serum. In tests using 30-40% serum, GLA and ALA killed tumor at concentrations of 2 mM and above.ConclusionsThe concentration threshold of 500 μM to 2 mM exhibited for antitumor activity by GLA and ALA is much higher than that observed in most previously reported cell culture studies but consistent with physiological concentrations found to kill tumor clinically and in animals. A mechanism of antitumor activity by unsaturated fatty acids through selective destabilization of the malignant plasma membrane is considered. An oral regimen is proposed for phase I clinical testing that could push the area under the curve for serum concentration of unbound unsaturated fatty acids over time to much higher levels than previously achieved for systemic administration and into the range that could yield antitumor response.

show abstract