Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells

Tsuma-Kaneko, Mitsuyo; Sawanobori, Masakazu; Kawakami, Shohei; Uno, Tomoko; Nakamura, Yoshihiko; Onizuka, Makoto; Ando, Kiyoshi; Kawada, Hiroshi

doi:10.1038/s41598-018-35730-8

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…The capacity of metal chelators to act as anticancer agents (and potentially as clinically effective treatment options) has been reported in various in vitro cancer models including malignant melanoma and leukemia [60,61]. During our study, a series of hydroxypyridinones-based analogues of L-mimosine were synthesized and their anticancer activity was evaluated against an in vitro model of human malignant melanoma.…”

Section: Discussionmentioning

confidence: 98%

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

et al. 2019

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The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.

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Section: Discussionmentioning

confidence: 98%

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

et al. 2019

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“…Hydrogen peroxide formation increased under the influence of high dose vitamin C and in the presence of an appropriate concentration of iron ions [35,36]. Further, Tsuma-Kaneko et al [37] suggested that this could exert anti-cancer effects. On the other hand, in patients with chronic lymphocytic leukaemia, vitamin C in a dose of 1000 mg/day had a positive influence on the incidence of infectious complications [38].…”

Section: Vitamin C Concentration and Plasma Pro-/antioxidant Capacitymentioning

confidence: 98%

Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women

Żychowska

Grzybkowska

Wiech

et al. 2020

IJMS

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Physical training and antioxidant supplementation may influence iron metabolism through reduced oxidative stress and subsequent lowering of mRNA levels of genes that are easily induced by this stress, including those responsible for iron homeostasis. Fifteen elderly women participated in our 12-week experiment, involving six weeks of training without supplementation and six weeks of training supported by oral supplementation of 1000 mg of vitamin C daily. The participants were divided into two groups (n = 7 in group 1 and n = 8 in group 2). In group 1, we applied vitamin C supplementation in the first six weeks of training, while in group 2 during the remaining six weeks of training. In both phases, the health-related training occurred three times per week. Training accompanied by vitamin C supplementation did not affect prooxidative/antioxidative balance but significantly decreased ferritin heavy chain (FTH) and ferritin light chain (FTL) mRNA in leukocytes (for FTH mRNA from 2^64.24 to 2^11.06, p = 0.03 in group 1 and from 2^60.54 to 2^16.03, p = 0.01 in group 2, for FTL mRNA from 2^20.22 to 2^4.53, p = 0.01 in group 2). We concluded that vitamin C supplementation might have caused a decrease in gene expression of two important antioxidative genes (FTH, FTL) and had no effect on plasma prooxidative/antioxidative balance.

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“…However, at present, it is rather a complex issue as many questions must be answered, including an optimal and still physiologically relevant iron 5 Oxidative Medicine and Cellular Longevity concentration to produce free radicals and decompose hydrogen peroxide. That study was supported by the recent work of Tsuma-Kaneko et al who showed that excess of iron decreased the pharmacological vitamin C-induced inhibition of survival of the human myeloid leukemia K562 cells in vitro through a decrease in H 2 O 2 level and depletion in the apoptotic pathway induced by the vitamin [81]. Moreover, iron excess reversed anticancer effects induced by vitamin C in vivo, so stimulation, not inhibition, of the K562 cell in mouse transplants was observed.…”

Section: Molecular Studiesmentioning

confidence: 57%

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

Pawłowska

Szczepańska

Błasiak

2019

Oxidative Medicine and Cellular Longevity

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Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose transport and ATP production resulting in energetic crisis and cell death. Vitamin C may change the metabolomic and epigenetic profiles of cancer cells, and activation of ten-eleven translocation (TET) proteins and downregulation of pluripotency factors by the vitamin may eradicate cancer stem cells. Metastasis, the main reason of cancer-related deaths, requires breakage of anatomical barriers containing collagen, whose synthesis is promoted by vitamin C. Vitamin C induces degradation of hypoxia-inducible factor, HIF-1, essential for the survival of tumor cells in hypoxic conditions. Dietary vitamin C may stimulate the immune system through activation of NK and T cells and monocytes. Pharmacological doses of vitamin C may inhibit cancer transformation in several pathways, but further studies are needed to address both mechanistic and clinical aspects of this effect.

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Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells

Cited by 15 publications

References 26 publications

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

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