European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects

Frontiers in Oncology
Tej H PatelM Cristina Kenney

Abstract

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mit...Continue Reading

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Citations

May 27, 2020·Biochemical Society Transactions·Sophie L PenmanAmy E Chadwick
May 31, 2020·Molecular Cancer Research : MCR·Luca X ZampieriPierre Sonveaux
Dec 29, 2020·IUBMB Life·Ana Victoria Lechuga-ViecoJosé Antonio Enríquez
Feb 23, 2021·Molecular Therapy. Nucleic Acids·Lei ZhangPeifeng Li
Sep 7, 2021·Frontiers in Genetics·Samantha W JonesAna Alfirevic

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Methods Mentioned

BETA
Reverse Transcription PCR
reverse transcription-PCR
acetylation

Software Mentioned

GraphPad
Pisces
Prism
GraphPad Prism
PASSed

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