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Published in: Medical Oncology 8/2021

01-08-2021 | Breast Cancer | Original Paper

Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug

Authors: Meysam Bakhshoudeh, Kayhan Mehdizadeh, Saman Hosseinkhani, Farangis Ataei

Published in: Medical Oncology | Issue 8/2021

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Abstract

Drug resistance is a multifactorial process involving a variety of mechanisms and genes. Taxane drug class like Docetaxel is not effective for all types’ breast cancers and presents a huge clinical challenge. To improve cancer treatment outcome, it is important to distinguish which proteins can kill the cancer cells and whether the expression levels of these proteins affect treatment. Cancer cells are wildly known to be protected from apoptosis, due to low level of apoptotic protease activating factor-1 (Apaf-1) compared with normal cells. Apaf-1 is an essential protein that defines whether cytochrome c released form mitochondria remains stable or degrades. According to this hypothesis, increasing of Apaf-1 expression in MCF7 breast cancer cells was performed and Docetaxel efficacy examined. The immunoassay techniques were used to investigate Apaf-1 and cytochrome c levels, and different apoptosis assay methods applied to better understand the effect of Apaf-1 expression levels in cellular response to apoptotic stimuli by Docetaxel. Our results determined that cytoplasmic cytochrome c level elevated along with increasing Apaf-1 and MCF7 cells were sensitised to Docetaxel, suggesting that loss of Apaf-1 may cause Docetaxel-resistance in breast cancer cells through less apoptosome formation. ROS level increased in cells transfected with Apaf-1 and induced mitochondrial permeability for cytochrome c release, which subsequently promoted apoptosome formation, intrinsic apoptosis and ATP depletion.
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Metadata
Title
Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug
Authors
Meysam Bakhshoudeh
Kayhan Mehdizadeh
Saman Hosseinkhani
Farangis Ataei
Publication date
01-08-2021
Publisher
Springer US
Published in
Medical Oncology / Issue 8/2021
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-021-01532-8

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