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

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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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Acknowledgements

This work was supported by the research council of Tarbiat Modares University and Iranian National Science Foundation (INSF, project 93043373).

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  1. Meysam Bakhshoudeh and Kayhan Mehdizadeh have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Meysam Bakhshoudeh, Kayhan Mehdizadeh, Saman Hosseinkhani & Farangis Ataei

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  1. Meysam Bakhshoudeh
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Bakhshoudeh, M., Mehdizadeh, K., Hosseinkhani, S. et al. Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug. Med Oncol 38, 88 (2021). https://doi.org/10.1007/s12032-021-01532-8

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  • DOI: https://doi.org/10.1007/s12032-021-01532-8

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