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Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins

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Abstract

Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.

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Acknowledgments

The financial support from the Ministry of Science and Technology and Department of Biotechnology-Boost to University Interdisciplinary Life science Departments for Education and Research (DBT-BUILDER) programme, New Delhi, Government of India is gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    R. Kamaraj Kennedy, V. Veena, P. Ravindra Naik & N. Sakthivel

  2. Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    Pragna Lakshmi & R. Krishna

  3. Department of Molecular Biology and Biochemistry, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    S. Sudharani

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  1. R. Kamaraj Kennedy
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Correspondence to N. Sakthivel.

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Kennedy, R.K., Veena, V., Naik, P.R. et al. Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins. Apoptosis 20, 858–868 (2015). https://doi.org/10.1007/s10495-015-1118-0

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  • DOI: https://doi.org/10.1007/s10495-015-1118-0

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