Hyperglycemia Promotes Chemoresistance Through the Reduction of the Mitochondrial DNA Damage, the Bax/Bcl-2 and Bax/Bcl-XL Ratio, and the Cells in Sub-G1 Phase Due to Antitumoral Drugs Induced-Cytotoxicity in Human Colon Adenocarcinoma Cells

Frontiers in Pharmacology
Loredana BergandiSophie Doublier

Abstract

Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies clearly indicate that the risk of several types of cancer is increased in diabetic patients and a number of cancer types have shown a higher mortality rate in patients with hyperglycemic associated pathologies. This scenario could be due, at least in part, to a lower efficacy of the cancer treatments which needs to be better investigated. Here, we evaluated the effects of a prolonged exposure to high glucose (HG) to the response to chemotherapy on human colon adenocarcinoma HT29 and LOVO cell lines. We observed that hyperglycemia protected against the decreased cell viability and cytotoxicity and preserved from the mitochondrial DNA lesions induced by doxorubicin (DOX) and 5-fluorouracil (5-FU) treatments by lowering ROS production. In HT29 cells the amount of intracellular DOX and its nuclear localization were not modified by HG incubation in terms of Pgp, BCRP, MRP1, 5 and 8 activity and gene expression. On the contrary, in LOVO cells, the amount of intracellular DOX was significantly decreased after a bolus of DOX in HG condition and the expression and activity of MPR1 was increased, suggesting that HG prom...Continue Reading

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Citations

Aug 21, 2019·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Jincheng YangJianying Zhang
Dec 4, 2019·Biological & Pharmaceutical Bulletin·Akihiro InamuraKoichi Sakurai
Aug 3, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Yueyue ChenZhiwei Sun
Oct 26, 2021·Frontiers in Oncology·Vivek Kumar SoniNaveen Kumar Vishvakarma

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Methods Mentioned

BETA
PCR
electrophoresis
Polymerase Chain Reaction
PCRs
RNAseA
flow cytometry
Assay
acetylation

Software Mentioned

CFX96 Touch TM
Quantity One
MassLynx
Multicycle
ImageJ
Atlas
CompuSyn

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