Dihydro-alpha-lipoic acid has more potent cytotoxicity than alpha-lipoic acid

Abstract

Alpha-lipoic acid has been shown to possess cancer-cell-killing activity via activation of the apoptosis pathway. In this study, the cytotoxic activities of alpha-lipoic and dihydro-alpha-lipoic acid were compared in HL-60 cells. The cell-killing activity of dihydro-alpha-lipoic acid was higher than that of alpha-lipoic acid. Both alpha-lipoic and dihydro-alpha-lipoic acid induced caspase-3 cleavage and internucleosomal DNA fragmentation in treated cells. On the other hand, apparent necrotic or late-stage apoptotic cell populations could be detected in dihydro-alpha-lipoic acid cells but not in those treated with alpha-lipoic acid. Moreover, dihydro-alpha-lipoic acid, but not alpha-lipoic acid, induced marked mitochondrial permeability transition. Antioxidants could not prevent dihydro-alpha-lipoic- or alpha-lipoic-acid-induced cell death. In addition, dihydro-alpha-lipoic and alpha-lipoic acid did not up-regulate cellular reactive oxygen level. These results indicated that dihydro-alpha-lipoic acid exerts more potent cytotoxicity than alpha-lipoic acid through different cytotoxic actions.

The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles

“…In support of our results, long time exposure to ALA results in increase of lipid peroxidation, mitochondrial damage and inhibition of glycogen synthesis [17,36]. Also, it has been shown that high dose of ALA could arrest cell cycles in some cells [35,55] or could provoke cell death through internucleosomal DNA fragmentation and caspase cleavage in numerous cancer cell lines [48,55,57]. Hence, it appears that high doses of ALA more than 100 uM are toxic for isolated preantral follicles.…”

“…This observation may give explanation about our finding which why increasing of ALA concentrations results in decrease developmental competence of isolated follicles. In addition, as previous mentioned, high dose of ALA in numerous cancers cell lines could induce apoptosis [35,48,55,57] which explicates, high degeneration rate of follicles in the presence of high concentrations of ALA.…”

“…Hence, addition of antioxidants to culture media would be rational to control excessive OS during in vitro culture of gametes or embryos, [12,22,30,40]. In this context, alpha-lipoic acid (ALA), (R)-5-(1,2-dithiolan-3-yl) pentanoic acid, is an important coenzyme of mitochondrial multienzyme complexes [14,41,42] and is well-known for its antioxidant rule in various biological processes [57]. ALA acts directly in scavenging of ROS, metal chelation and indirectly in recycling of other intracellular antioxidants [41,42].…”

Induction of Apoptotic Cell Death in HL-60 Cells by Jacaranda Seed Oil Derived Fatty Acids

“…Our previous data showed internucleosomal DNA fragmentation as one of the features of apoptosis in HL-60 cells 23 . In the present study, an increase in the sub-G1 population was observed Fig.…”

Influence of α-lipoic acid on liver glutathione system of healthy and ehrlich ascites carcinoma transplanted mice

“…Последние исследования сообщают о её противоопухолевых эффектах [3][4][5][6][7]. ЛК образуется в организме и присутствует в следовых количествах.…”