Disulfiram oxy-derivatives induce entosis or paraptosis-like death in breast cancer MCF-7 cells depending on the duration of treatment

Solovieva, Marina E.; Shatalin, Yuri V.; Odinokova, Irina; Krestinina, Olga; Baburina, Yulia; Mishukov, Artem; Lomovskaya, Yana V.; Павлик, Л. Л.; Mikheeva, I. B.; Holmuhamedov, Ekhson; Акатов, В. С.

doi:10.1016/j.bbagen.2022.130184

Cited by 14 publications

(16 citation statements)

References 71 publications

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“…Our previous results have indicated that combinations of HOCbl with GSH, NAC, AA [31], DTT [32], and DDC [38,39,51] produce a cytotoxic effect on HEp-2 cells. It was shown using an oxygen electrode that the oxidation of thiols [31,32] and AA [31] catalyzed by H2OCbl + /HOCbl is accompanied by the accumulation of hydrogen peroxide in culture medium.…”

Section: Discussionmentioning

confidence: 96%

“…Our previous results indicate that combinations of HOCbl with GSH, NAC, DTT, and АА lead to apoptotic death in cancer cells [31,32,37]. At the same time, a combination of HOCbl with DDC leads to entosis [38] and/or paraptosis-like cell death [38,39]. For a more complete understanding of mechanisms underlying the effects of cobalamin-reducing agent combinations, first of all a deeper insight into ongoing chemical processes is needed.…”

Section: Introductionmentioning

confidence: 99%

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A Comparative Study of ROS Production and Cytotoxicity Induced by Combinations of Thiols with HOCbl and CNCbl

Shatalin¹,

Shubina²,

Solovieva³

et al. 2022

Preprint

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Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by ROS production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. It was discussed how these differences may explain different levels of ROS production and cytotoxicity induced by combinations of thiols with HOCbl and CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved and might be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component. In addition, these data may be useful for a better understanding of mechanisms underlying induction of different types of death of cancer cells and in a search for new targets for anticancer therapy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

A Comparative Study of ROS Production and Cytotoxicity Induced by Combinations of Thiols with HOCbl and CNCbl

Shatalin¹,

Shubina²,

Solovieva³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Our previous results have indicated that combinations of HOCbl with GSH, NAC, AA [ 31 ], DTT [ 32 ], and DDC [ 38 , 39 , 62 ] produce a cytotoxic effect on HEp-2 cells. It was shown using an oxygen electrode that the oxidation of thiols [ 31 , 32 ] and AA [ 31 ] catalyzed by H 2 OCbl + /HOCbl is accompanied by the accumulation of hydrogen peroxide in culture medium.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous results indicate that combinations of HOCbl with GSH, NAC, DTT, and ascorbic acid (AA) lead to apoptotic death in cancer cells [ 31 , 32 , 37 ]. At the same time, a combination of HOCbl with sodium diethyldithiocarbamate (DDC) leads to entosis [ 38 ] and/or paraptosis-like cell death [ 38 , 39 ]. For a more complete understanding of mechanisms underlying the effects of cobalamin-reducing agent combinations, a deeper insight into ongoing chemical processes is needed.…”

Section: Introductionmentioning

confidence: 99%

Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins

Shatalin

Shubina

Solovieva

et al. 2022

IJMS

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Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by reactive oxygen species (ROS) production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. HOCbl increased the rate of oxidation of thiols to a greater extent than CNCbl, but quenched ROS in combination with certain thiols. Oxidation catalyzed by CNCbl was generally slower. Yet, the absence of ROS quenching resulted in their higher accumulation. The aforementioned results might explain a more pronounced cytotoxicity induced by combinations of thiols with CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved. Our results might also be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component.

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“…The fate of the inner cell in entosis can either be cell survival ("vital" entosis) or death ("lethal" entosis) [1,2]. Entosis has been reported in numerous cancers [2][3][4][5][6][7][8][9][10][11][12][13]. Breast cancer (BC) seems to be especially entosis-competent and entotic figures have been detected in both primary tumors, as well as metastatic lesions [6][7][8][9][10]14,15].…”

Section: Introductionmentioning

confidence: 99%

Fate of Entosis: From the Beginning to the End in Untreated Advanced Breast Cancer

Dziuba,

Gawel,

Tyrna

et al. 2023

IJMS

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Homotypic entosis is a phenomenon in which one cancer cell invades a neighboring cancer cell and is closed entirely within its entotic vacuole. The fate of entosis can lead to inner cell death or survival. Recent evidence draws attention to entosis as a novel prognostic marker in breast cancer. Nevertheless, little is known about the quantity and quality of the process of entosis in human cancer specimens. Here, for the first time, we analyze the frequency of entotic figures in a case of NOS (Non-Other Specified) breast cancer with regard to location: the primary tumor, regional lymph node, and distant metastasis. For the identification of entotic figures, cells were stained using hematoxylin/eosin and assessed using criteria proposed by Mackay. The majority of entotic figures (65%) were found in the lymph node, 27% were found in the primary tumor, and 8% were found in the far metastasis. In the far metastases, entotic figures demonstrated an altered, atypic morphology. Interestingly, in all locations, entosis did not show any signs of cell death. Moreover, the slides were stained for E-cadherin or Ki67, and we identified proliferating (Ki67-positive) inner and outer entotic cells. Therefore, we propose additional criteria for the identification of pro-survival entotic structures in diagnostic histopathology.

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Disulfiram oxy-derivatives induce entosis or paraptosis-like death in breast cancer MCF-7 cells depending on the duration of treatment

Cited by 14 publications

References 71 publications

A Comparative Study of ROS Production and Cytotoxicity Induced by Combinations of Thiols with HOCbl and CNCbl

A Comparative Study of ROS Production and Cytotoxicity Induced by Combinations of Thiols with HOCbl and CNCbl

Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins

Fate of Entosis: From the Beginning to the End in Untreated Advanced Breast Cancer

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