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 u...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2019-08, Vol.33 (8), p.e22350-n/a
Main Authors: Mansour, Mohammed A., Ibrahim, Wafaa M., Shalaan, Eman S., Salama, Afrah F.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - toxicity
Apoptosis
Arsenic
Arsenic trioxide
Arsenic Trioxide - administration & dosage
Arsenic Trioxide - toxicity
Ascites
autophagy
beclin 1
Breast cancer
Breast carcinoma
Cancer
Carcinoma, Ehrlich Tumor - pathology
Cell death
Cell Line, Tumor
Cell Survival - drug effects
Chemoresistance
Chemotherapy
Cisplatin
Cisplatin - administration & dosage
Cisplatin - toxicity
Drug Synergism
Drugs
Ehrlich ascites carcinoma
Female
Hexokinase
Hexokinase - antagonists & inhibitors
Mice
Mice, Inbred BALB C
Mortality
Oxidative stress
Oxidative Stress - drug effects
Viability
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Summary: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.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.22350