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5-farnesyloxycoumarin: a potent 15-LOX-1 inhibitor, prevents prostate cancer cell growth

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Abstract

In this study, the activity of 15-LOX-1 was first evaluated in two prostate cancer cell lines PC3 and DU145. Considering the enzyme inhibitory potency of 5-farnesyloxycoumarin (5f), the cytotoxic effects of this compound was studied in PC3, DU145 and HFF3 (normal cell line) by MTT assay. Since 5f was more effective on PC3 cells, this cell line was used for further explorations. The chromatin condensation and DNA damage were studied by DAPI staining and comet assay, respectively and cell cycle analysis was performed by propidium iodide staining. Results indicated that 15-LOX-1 activity was very low in DU145 cells. Moreover, PC3 cells were more sensitive to 5f as compared to DU145 cancerous cells, while no significant effect was observed on normal HFF3 cells. Interestingly, the IC50 values of 5f on PC3 cells were similar to cisplatin. DAPI staining showed that 5f induced chromatin condensation in 63 % of PC3 cells. Comet assay also demonstrated 53 % “DNA in tail” for PC3 cells. Finally, 5f induced G0/G1 arrest in PC3 cell cycle. These findings suggest that cytotoxic effects of 5f might be due to the inhibition of 15-LOX-1 in PC3 cell line and, it can be introduced as a potent anticancer compound.

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Acknowledgments

This work was supported by a grant from Ferdowsi University of Mashhad. The authors would like to thank Dr. Behnam—Rassouli, Mr. Malaekeh—Nikouei and Mr. Nakhaei for their excellent support and technical help.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Ala Orafaie, Ahmad Reza Bahrami, Saffiyeh Saboormaleki & Maryam M. Matin

  2. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamid Sadeghian

  3. Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Ahmad Reza Bahrami & Maryam M. Matin

  4. Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamid Sadeghian

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  1. Ala Orafaie
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  2. Hamid Sadeghian
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  3. Ahmad Reza Bahrami
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  4. Saffiyeh Saboormaleki
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  5. Maryam M. Matin
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Correspondence to Maryam M. Matin.

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Orafaie, A., Sadeghian, H., Bahrami, A.R. et al. 5-farnesyloxycoumarin: a potent 15-LOX-1 inhibitor, prevents prostate cancer cell growth. Med Chem Res 26, 227–234 (2017). https://doi.org/10.1007/s00044-016-1737-1

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  • DOI: https://doi.org/10.1007/s00044-016-1737-1

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