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

Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells
Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells
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 As2 O3 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 As2 O3 with cisplatin synergistically enhanced these effects and alleviated oxidative stress often encountered in As2 O3 treatment. Altogether, our data provide direct evidence that inhibition of hexokinase activity and induction of autophagic cell death are mediating the antineoplastic effects of As2 O3 and cisplatin. Our findings raise the potential of combining As2 O3 with cisplatin as an approach to augment cisplatin-induced cell death and combat cisplatin chemoresistance in cancer.
1099-0461
Mansour, Mohammed
03d901e1-959e-4c7d-acc6-33c6a4b129f7
Ibrahim, Wafaa
2e95c0dc-45c6-4432-b6ed-ff85650e7fee
Shalaan, Eman
91c9558c-5607-4db3-b4be-cceb4a489319
Salama, Afrah F.
5558e250-308a-4e94-9efd-0ece23c88e01
Mansour, Mohammed
03d901e1-959e-4c7d-acc6-33c6a4b129f7
Ibrahim, Wafaa
2e95c0dc-45c6-4432-b6ed-ff85650e7fee
Shalaan, Eman
91c9558c-5607-4db3-b4be-cceb4a489319
Salama, Afrah F.
5558e250-308a-4e94-9efd-0ece23c88e01

Mansour, Mohammed, Ibrahim, Wafaa, Shalaan, Eman 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 (8), [e22350]. (doi:10.1002/jbt.22350).

Record type: Article

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 As2 O3 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 As2 O3 with cisplatin synergistically enhanced these effects and alleviated oxidative stress often encountered in As2 O3 treatment. Altogether, our data provide direct evidence that inhibition of hexokinase activity and induction of autophagic cell death are mediating the antineoplastic effects of As2 O3 and cisplatin. Our findings raise the potential of combining As2 O3 with cisplatin as an approach to augment cisplatin-induced cell death and combat cisplatin chemoresistance in cancer.

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More information

Accepted/In Press date: 7 May 2019
e-pub ahead of print date: 31 May 2019
Published date: August 2019

Identifiers

Local EPrints ID: 433901
URI: http://eprints.soton.ac.uk/id/eprint/433901
ISSN: 1099-0461
PURE UUID: 02612285-e225-4f1d-b42f-c87fd5db2b22

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Date deposited: 05 Sep 2019 16:30
Last modified: 16 Mar 2024 02:51

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Contributors

Author: Mohammed Mansour
Author: Wafaa Ibrahim
Author: Eman Shalaan
Author: Afrah F. Salama

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