Combined Vitamins B12b and C Induce the Glutathione Depletion and the Death of Epidermoid Human Larynx Carcinoma Cells HEp-2

Акатов, В. С.; Evtodienko, Yury V.; Leshchenko, Violetta V.; Теплова, В. В.; Potselueva, M. M.; Kruglov, Alexey G.; Lezhnev, E. I.; Yakubovskaya, Raisa I.

doi:10.1023/a:1010386102562

Cited by 11 publications

(4 citation statements)

References 5 publications

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“…It has been shown earlier that cobalamins are capable of catalyzing the formation of reactive oxygen species in the presence of natural reducing agents, e.g., ascorbate and thiols, which leads to oxidative stress [13][14][15]. We have found that hydroxycobalamin (B 12b ) in combination with ascorbate and thiol antioxidants GSH, NAC, and DTT catalyzes the formation and accumulation of hydrogen peroxide in medium, inducing single-and double-strand DNA breaks and the damage to lysosomes, which ultimately led to apoptoptic cell death [16][17][18][19]. Recently, we have shown that B 12b catalyzes the oxidation of diethyldithiocarbamate (DDC), a member of another group of thiol-containing substances, namely dithiocarbamates (DTC) [20].…”

Section: Introductionmentioning

confidence: 99%

Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells

et al. 2020

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We have shown that hydroxycobalamin (vitamin B12b) increases the toxicity of diethyldithiocarbamate (DDC) to tumor cells by catalyzing the formation of disulfiram (DSF) oxi-derivatives. The purpose of this study was to elucidate the mechanism of tumor cell death induced by the combination DDC + B12b. It was found that cell death induced by DDC + B12b differed from apoptosis, autophagy, and necrosis. During the initiation of cell death, numerous vacuoles formed from ER cisterns in the cytoplasm, and cell death was partially suppressed by the inhibitors of protein synthesis and folding, the IP3 receptor inhibitor as well as by thiols. At this time, a short-term rise in the expression of ER-stress markers BiP and PERK with a steady increase in the expression of CHOP were detected. After the vacuolization of the cytoplasm, functional disorders of mitochondria and an increase in the generation of superoxide anion in them occurred. Taken together, the results obtained indicate that DDC and B12b used in combination exert a synergistic toxic effect on tumor cells by causing severe ER stress, extensive ER vacuolization, and inhibition of apoptosis, which ultimately leads to the induction of paraptosis-like cell death.

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Section: Introductionmentioning

confidence: 99%

Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells

et al. 2020

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“…Modification of one of the constituents (i.e. brominated VK 3 ) or replacement of the VK 3 with any number of constituents (arsenic trioxide, benzoquinones, coenzyme Q10, doxorubicin, lipoic acid, resveratrol, vitamin B12, Vitamin E and others) [67,[80][81][82][83][84][85].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antitumor Activity of Vitamins C and K3 on Human Bladder Cancer Cell Lines

McGuire¹,

Jamison²,

Gilloteaux³

et al. 2013

JCT

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Exponentially growing cultures of human bladder tumor cells (RT4 and T24) were treated with Vitamin C (VC) alone, Vitamin K₃ (VK₃) alone, or with a VC:VK₃ combination continuously for 5 days or treated with vitamins for 1 h, washed with PBS and then incubated in culture medium for 5 days. Co-administration of the vitamins enhanced the antitumor activity 12- to 24-fold for the RT-4 cells and 6- to 41-fold for the T24 cells. Flow cytometry of RT4 cells exposed to the vitamins revealed a growth arrested population and a population undergoing cell death. Growth arrested cells were blocked near the G₀/G₁-S-phase interface, while cell death was due to autoschizis. Catalase treatment abrogated both cell cycle arrest and cell death which implicated hydrogen peroxide (H₂O₂) in these processes. The H₂O₂ production resulted in a moderate increase in lipid peroxidation and depletion of cell thiol levels. Analysis of cellular ATP levels revealed a transient increase in ATP production for VC and the VC:VK₃ combination, but decreased ATP levels following VK₃ treatment. Lipid peroxidation, thiol depletion and ATP modulation occurred at a 17-fold lower concentration in the vitamin combination than with either vitamin alone. These results suggested that the increased cytotoxicity of the vitamin combination was due to redox cycling and increased oxidative stress.

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“…It is established that antioxidants combined with metals of variable valence may form prooxidant catalytic systems. An example of such a system is ascorbate combined with organic complexes of copper or cobalt, such as vitamin B 12b or cobalt phthalocyanines, which were used as antitumor agents during the past years [2][3][4][5][6][7]. However, it is unclear how thiols may serve as prooxidants in combination with vitamin B 12b .…”

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confidence: 99%

“…The agents studied were added 24 h after the plating 350 000 HEp-2 cells in T25 flasks. The calibration was performed by addition of H 2 O 2 into the experimental chamber after catalase [7].…”

mentioning

confidence: 99%

Prooxidant and Cytotoxic Effects of Thiols Combined with Vitamin B12b

et al. 2005

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Combined Vitamins B12b and C Induce the Glutathione Depletion and the Death of Epidermoid Human Larynx Carcinoma Cells HEp-2

Cited by 11 publications

References 5 publications

Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells

Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells

Synergistic Antitumor Activity of Vitamins C and K3 on Human Bladder Cancer Cell Lines

Prooxidant and Cytotoxic Effects of Thiols Combined with Vitamin B12b

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