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The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines

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Abstract

β-blockers having specific affinities to β-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of β-1 selective esmolol, β-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the β-blockers at 150–250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the β-blockers are considered, it seems that β-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.

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Acknowledgements

This study was supported by Grants from The Scientific and Technological Research Council of Turkey (TUBİTAK) with 218Z071 numbered project.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Arts and Sciences, Pamukkale University, Kinikli, 20070, Denizli, Turkey

    Berna Kavakcıoğlu Yardımcı

  2. Department of Biology, Faculty of Science, Ataturk University, Yakutiye, 25030, Erzurum, Turkey

    Fatime Geyikoglu, Ferhunde Aysin, Kubra Koc & Nihal Simsek Ozek

  3. East Anatolian High Technology Research and Application Center (DAYTAM), Ataturk University, Yakutiye, 25030, Erzurum, Turkey

    Ferhunde Aysin & Nihal Simsek Ozek

  4. Department of Physiology, Faculty of Medicine, Pamukkale University, Kinikli, 20020, Denizli, Turkey

    Vural Küçükatay

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  1. Berna Kavakcıoğlu Yardımcı
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  3. Ferhunde Aysin
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Contributions

BKY conceived, designed, and supervised the project, performed the experiments, computations, analyzed the data and wrote the manuscript, provided financial support and final approval of the manuscript. FG, FA and KK contributed to the study conception and design, performed the experiments and reviewed the manuscript. NSO performed the experiments, computations, analyzed the data and reviewed the manuscript. VK performed the computations, analyzed the data, reviewed the manuscript and provided environmental support.

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Correspondence to Berna Kavakcıoğlu Yardımcı.

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Kavakcıoğlu Yardımcı, B., Geyikoglu, F., Aysin, F. et al. The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines. Mol Biol Rep 48, 4009–4019 (2021). https://doi.org/10.1007/s11033-021-06409-7

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  • DOI: https://doi.org/10.1007/s11033-021-06409-7

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