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Prodigiosin isolated from cell wall of Serratia marcescens alters expression of apoptosis-related genes and increases apoptosis in colorectal cancer cells

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Abstract

Colorectal cancer remains often refractory to classic therapies. In consequence, the search for new anti-tumor agents with minimal toxicity is of particular interest in colon cancer treatment. Prodigiosin as a secondary metabolite of Serratia marcescens induces apoptosis in various kinds of cancer cells with low toxicity on normal cells. In the present study, we evaluated the effect of prodigiosin on proliferation and expression of apoptotic-related genes in HT-29 cells. Malignant cells were treated to various concentrations of prodigiosin and proliferation rate, survivin, Bcl-2, Bax and Bad mRNA levels, caspase 3 activation and apoptosis were evaluated by different cellular and molecular techniques. Treatment of cells with increasing concentration of prodigiosin decreased significantly cell proliferation in a dose- and time-dependent manner. Following 48-h treatment, growth rate was measured to be 77 ± 6.8, 41.3 ± 3.1 and 46 ± 6.3 % for 100, 400 and 600 nM prodigiosin, respectively, compared to untreated cells. This molecule induced 61.7, 90 and 89 % decrease in survivin mRNA level as well as 1.9-, 2.8- and 2.2-fold increase in caspase 3 activation for indicated concentrations of prodigiosin, respectively. The level of Bcl-2 mRNA was inversely proportional to Bax and Bad mRNA levels. Low mRNA levels of Bcl-2 combined with high levels of Bax and Bad mRNAs were correlated to higher apoptosis rate in treated cells. Our data suggest that prodigiosin-induced apoptosis may ascribe to Bcl-2 and survivin inhibition in HT-29 cells and these genes may provide promising molecular targets of prodigiosin. Collectively, prodigiosin may have a great potential for colorectal cancer-directed therapy.

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Acknowledgments

The authors herein express their great appreciation for the financial support received from Iran National Science Foundation (INSF).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Science, Islamic Azad University, Urmia Branch, Urmia, Iran

    Ramin Hassankhani

  2. Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran

    Mohammad Reza Sam

  3. Department of Histology and Embryology, Faculty of Science, Urmia University, Urmia, Iran

    Mohammad Reza Sam & Prinaz Ahangar

  4. Royan Stem Cell Technology Company, West Azarbaijan Cord Blood Bank, Urmia, Iran

    Mohammad Reza Sam

  5. Young Researchers and Elite Club, Islamic Azad University, Urmia Branch, Urmia, Iran

    Mohammad Esmaeilou

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  1. Ramin Hassankhani
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Correspondence to Mohammad Reza Sam.

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Hassankhani, R., Sam, M.R., Esmaeilou, M. et al. Prodigiosin isolated from cell wall of Serratia marcescens alters expression of apoptosis-related genes and increases apoptosis in colorectal cancer cells. Med Oncol 32, 366 (2015). https://doi.org/10.1007/s12032-014-0366-0

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