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Apoptosis

, Volume 20, Issue 6, pp 858–868 | Cite as

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

  • R. Kamaraj Kennedy
  • V. Veena
  • P. Ravindra Naik
  • Pragna Lakshmi
  • R. Krishna
  • S. Sudharani
  • N. SakthivelEmail author
Original Paper

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.

Keywords

Phenazine-1-carboxamide Cytotoxic p53 Bcl-2 family proteins Caspase-3 

Notes

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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • R. Kamaraj Kennedy
    • 1
  • V. Veena
    • 1
  • P. Ravindra Naik
    • 1
  • Pragna Lakshmi
    • 2
  • R. Krishna
    • 2
  • S. Sudharani
    • 3
  • N. Sakthivel
    • 1
    Email author
  1. 1.Department of Biotechnology, School of Life SciencesPondicherry UniversityPuducherryIndia
  2. 2.Centre for Bioinformatics, School of Life SciencesPondicherry UniversityPuducherryIndia
  3. 3.Department of Molecular Biology and Biochemistry, School of Life SciencesPondicherry UniversityPuducherryIndia

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