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The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity

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dc.contributor.author Begimbetova, Dinara
dc.contributor.author Burska, Agata N.
dc.contributor.author Baltabekova, Aidana
dc.contributor.author Kussainova, Assiya
dc.contributor.author Kukanova, Assiya
dc.contributor.author Fazyl, Fatima
dc.contributor.author Ibragimova, Milana
dc.contributor.author Manekenova, Kenzhekyz
dc.contributor.author Makishev, Abay
dc.contributor.author Bersimbaev, Rakhmetkazhi I.
dc.contributor.author Sarbassov, Dos D.
dc.date.accessioned 2024-09-18T04:35:32Z
dc.date.available 2024-09-18T04:35:32Z
dc.date.issued 2024
dc.identifier.citation Begimbetova, D.; Burska, A.N.; Baltabekova, A.; Kussainova, A.; Kukanova, A.; Fazyl, F.; Ibragimova, M.; Manekenova, K.; Makishev, A.; Bersimbaev, R.I.; et al. The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity. Int. J. Mol. Sci. 2024, 25, 2531. https://doi.org/10.3390/ ijms2505253 ru
dc.identifier.issn 1422-0067
dc.identifier.other doi.org/10.3390/ijms25052531
dc.identifier.uri http://rep.enu.kz/handle/enu/16547
dc.description.abstract The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its highdose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in KrasG12D-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings. ru
dc.language.iso en ru
dc.publisher International Journal of Molecular Sciences ru
dc.relation.ispartofseries Volume 25;Issue 5
dc.subject vitamin C (VC) or ascorbic acid ru
dc.subject D-Isoascorbic acid (D-VC) ru
dc.subject L-ascorbic acid (L-VC) ru
dc.subject toxicity ru
dc.subject reactive oxidative species (ROS) ru
dc.title The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity ru
dc.type Article ru


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