Next Article in Journal
Chemical Constituents from Fraxinus hupehensis and Their Antifungal and Herbicidal Activities
Previous Article in Journal
Kinetic, Thermodynamic, and Crystallographic Studies of 2-Triazolylthioacetamides as Verona Integron-Encoded Metallo-β-Lactamase 2 (VIM-2) Inhibitor
Open AccessArticle

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

1
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia
2
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 69; https://doi.org/10.3390/biom10010069
Received: 15 December 2019 / Revised: 29 December 2019 / Accepted: 30 December 2019 / Published: 1 January 2020
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. View Full-Text
Keywords: hydroxycobalamin; vitamin B12b; diethyldithiocarbamate; synergism; cytotoxicity; endoplasmic reticulum; ER-stress; cytoplasm vacuolization; paraptosis-like cell death hydroxycobalamin; vitamin B12b; diethyldithiocarbamate; synergism; cytotoxicity; endoplasmic reticulum; ER-stress; cytoplasm vacuolization; paraptosis-like cell death
Show Figures

Graphical abstract

MDPI and ACS Style

Solovieva, M.; Shatalin, Y.; Fadeev, R.; Krestinina, O.; Baburina, Y.; Kruglov, A.; Kharechkina, E.; Kobyakova, M.; Rogachevsky, V.; Shishkova, E.; Akatov, V. Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells. Biomolecules 2020, 10, 69. https://doi.org/10.3390/biom10010069

AMA Style

Solovieva M, Shatalin Y, Fadeev R, Krestinina O, Baburina Y, Kruglov A, Kharechkina E, Kobyakova M, Rogachevsky V, Shishkova E, Akatov V. Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells. Biomolecules. 2020; 10(1):69. https://doi.org/10.3390/biom10010069

Chicago/Turabian Style

Solovieva, Marina; Shatalin, Yuri; Fadeev, Roman; Krestinina, Olga; Baburina, Yulia; Kruglov, Alexey; Kharechkina, Ekaterina; Kobyakova, Margarita; Rogachevsky, Vadim; Shishkova, Elena; Akatov, Vladimir. 2020. "Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells" Biomolecules 10, no. 1: 69. https://doi.org/10.3390/biom10010069

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop