Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells

Journal article

Mansour, Mohammed A, Ibrahim, Wafaa M, Shalaan, Eman S and Salama, Afrah F (2019). Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells. Journal of biochemical and molecular toxicology. 33, pp. e22350-e22350. https://doi.org/10.1002/jbt.22350
AuthorsMansour, Mohammed A, Ibrahim, Wafaa M, Shalaan, Eman S and Salama, Afrah F
Abstract

Hexokinase‐2 is overexpressed in several carcinomas including breast cancer to sustain energy for rapidly dividing cells and associates with chemoresistance. However, the impact of chemo drugs (alone or in combination) on hexokinase activity and autophagic cell death is unclear. In this report, we used an in vivo murine adenocarcinoma model to validate the effects of As2O3 and cisplatin on hexokinase activity and autophagic cancer cell death. We found that the two drugs inhibit hexokinase activity and induce autophagic marker, beclin 1 expression. Interestingly, combining As2O3 with cisplatin synergistically enhanced these effects and alleviated oxidative stress often encountered in As2O3 treatment. Altogether, our data provide direct evidence that inhibition of hexokinase activity and induction of autophagic cell death are mediating the antineoplastic effects of As2O3 and cisplatin. Our findings raise the potential of combining As2O3 with cisplatin as an approach to augment cisplatin‐induced cell death and combat cisplatin chemoresistance in cancer.

Year2019
JournalJournal of biochemical and molecular toxicology
Journal citation33, pp. e22350-e22350
PublisherWiley
Digital Object Identifier (DOI)https://doi.org/10.1002/jbt.22350
Publication dates
Print31 May 2019
Publication process dates
Accepted07 May 2019
Deposited10 Aug 2020
Accepted author manuscript
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Open
Additional information

This is the peer reviewed version of the following article: Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells, which has been published in final form at https://doi.org/10.1002/jbt.22350. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Version

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