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Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines

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Abstract

Background

Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines.

Method

The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay). Fluorochrome staining (acridine orange/ethidium bromide double staining) and DNA fragmentation by the diphenylamine method were used to investigate the effects of most potent compounds on the process of apoptosis in breast cancer cell lines. To determine the mechanism of apoptosis, ROS and NOX production in treated breast cancer cells with compounds was evaluated.

Results

The cytotoxicity data of tested compounds demonstrate these compounds had varying degree of toxicity. Compound 7h was the most potent compound with IC50 = 1.8 ± 0.6 µg/mL against T-47D cell line. Analyses of the compounds treated (MCF-7, MDA-MB-231, and T-47D) cells by acridine orange/ethidium bromide double staining and DNA fragmentation by the diphenylamine method showed that the synthetic compounds induce apoptosis in the cells. A significant increase in ROS production was observed in T-47D cells treated with IC50 value of compound 7g. Incubation with IC50 value of synthetic compounds increased the NOX production in cell lines, especially T-47D cells.

Conclusion

Our results show that most compounds have a significant anti-proliferative activity against six human cancer cell lines. The observations confirm that chromen derivatives have induced the cell death through apoptosis.

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Acknowledgments

This research has been supported by a grant from Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Mahboobeh Pordeli & Sussan Kabudanian Ardestani

  2. Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Nakhjiri & Alireza Foroumadi

  3. Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, P. O. Box 3353-5111, Iran

    Maliheh Safavi

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  1. Mahboobeh Pordeli
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  2. Maryam Nakhjiri
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Correspondence to Maliheh Safavi.

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Pordeli, M., Nakhjiri, M., Safavi, M. et al. Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines. Breast Cancer 24, 299–311 (2017). https://doi.org/10.1007/s12282-016-0704-5

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  • DOI: https://doi.org/10.1007/s12282-016-0704-5

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