Cytotoxic activity of Prodigiosin of Serratia marcescens on cancer cells
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shahrzad salmanian,1,* Hamidreza Mollasalehi ,2
1. Department of Cellular and Molecular Biology, Faculty of Modern Science and Technology, Islamic Azad University, Medical Sciences Branch, Tehran, Iran
2. Department of Microbiology and Microbial Biotechnology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran
- Introduction: Cancer and malignancies are the main cause of fatalities for decades around the world. Some apoptosis-targeting drugs have been recently developed against tumor cells with great potential for cancer therapy. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosene = PGA) is a natural red pigment produced by Serratia marcescens comprises a common 4-methoxy, 2-2 bipyrrole ring which induces apoptosis in different types of cancer cells with low toxicity on normal cells. Recent studies have focused on the effect of prodigiosin on the apoptotic-related gene expression in various human cancer cells, such as human breast cancer (T47D) and human colon adenocarcinoma (HT-29) cells. Malignant cells have been treated with different prodigiosin concentrations and different molecular and cellular methods have been used for evaluating Caspase 3 activation and apoptosis.
- Methods: .
- Results: Therapy of the cells via expanding prodigiosin concentrations remarkably reduced the growth of cells in a time and dose-dependent manner. The amount of proapoptotic markers, such as caspase-3, Bax, and Bad mRNA versus the amount of anti-apoptotic markers, such as Survivin, and Bcl-2, specifies the cell resistor to apoptosis after exposure to prodigiosin. The levels of Survivin protein are controversary to the levels of caspase-3 protein in a cell. Low Survivin levels with high caspase-3 protein levels showed a correlation with higher rates of apoptosis in treated cells while the MMP-9 protein levels, involved in the development of several human malignancies, showed an inverse relationship with levels of caspase-3 protein. Low protein levels of MMP-9 with high caspase-3 protein levels showed a correlation with higher rates of apoptosis in cells treated with prodigiosin. Furthermore, the results illustrated that prodigiosin treatment is able to decrease Bcl-2, anti-apoptotic proteins, expression at demonstrated concentrations in comparison with untreated cells. Compared to Bcl-2 mRNA and Survivin levels, prodigiosin increased the expression of the Bad and Bax genes. Caspase-3 activation was significantly enhanced along with a rise in the prodigiosin doses in the treatment of tumor cells.
- Conclusion: The intestinal microbiota of insects has become a key area of interest in recent years. One of the bioactivity secondary metabolites produced by Serratia marcescens is recognized for its capability of generating plenty of secondary metabolites. It has been demonstrated that there is a relationship between prodigiosin and inhibiting the growth of cancer cells by apoptosis induction mechanism. Therefore, prodigiosin could be used in the new generation of anticancer factors. Finding the prodigiosin mechanism on apoptosis induction and recognition of its molecular spot could provide valuable insight into its available applications in cancer therapy and benefit. However, the function of prodigiosin in apoptosis mechanisms needs further research.
- Keywords: Prodigiosin _ Serratia marcescens _ Cytotoxicity _ apoptosis_ anticancer
