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Caesalpinia sappan L. heartwood ethanolic extract exerts genotoxic inhibitory and cytotoxic effects

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Abstract

Brazilin and brazilein, the major compounds of Caesalpinia sappan L. (CS) have been reported to possess antioxidant and cytotoxic activities and could potentially be used as an antigenotoxic as well as an anticancer. This study was conducted to investigate the cytotoxic and antigenotoxic effects of CS ethanolic extract (CEE). In vivo mammalian micronucleus test of CEE at the dose of 500 mg/kg BW and 1000 mg/kg BW decreased the number of MNPCE and increased the ratio of PCE to NCE meaning that CEE performed antigenotoxic effect in an in vivo model. In contrast, CEE and doxorubicin (DOXO) performed cytotoxic effect on CHO-K1 cells under MTT assay with IC50 values of 67 μg/mL and 6 μM, respectively. Interestingly, treatment of CEE in combination with DOXO and H2O2 as genotoxic inducer decreased intracellular ROS levels. In addition, in vitro genotoxicity study by using cytokinesis-block micronucleus (CBMN) assay, both of Giemsa staining and flow cytometric analysis showed that the treatment of CEE increased the number of micronuclei and correlated with apoptotic induction results. Moreover, the combination of CEE and DOXO induced cells accumulation in Sub-G1 and G2/M phase. In conclusion, CEE performed antigenotoxic effect in an in vivo model and cytotoxic effect on CHO-K1 cells.

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Acknowledgements

This study was financially supported by Research Grant from The Ministry of Research, Technology, and Higher Education of the Republic of Indonesia. We would like to especially thank Prof. Masashi Kawaichi, Laboratory of Gene Function in Animal, Graduate School of Biological Science, Nara Institute of Science and Technology (NAIST) for providing the cell culture.

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Authors and Affiliations

  1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia

    Edy Meiyanto, Beni Lestari, Raisatun Nisa Sugiyanto, Riris Istighfari Jenie & Rohmad Yudi Utomo

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia

    Edy Meiyanto, Riris Istighfari Jenie & Ediati Sasmito

  3. Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia

    Retno Murwanti

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  1. Edy Meiyanto
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  2. Beni Lestari
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  3. Raisatun Nisa Sugiyanto
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Correspondence to Edy Meiyanto.

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The authors declare that they have no conflict of interest.

Statement on the welfare of animals

All procedures performed in studies involving animals were in accordance with the ethical standards from Universitas Gadjah Mada with the approval number 462/KEC-LPPT/IV/2016 at which the studies were conducted.

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Meiyanto, E., Lestari, B., Sugiyanto, R.N. et al. Caesalpinia sappan L. heartwood ethanolic extract exerts genotoxic inhibitory and cytotoxic effects. Orient Pharm Exp Med 19, 27–36 (2019). https://doi.org/10.1007/s13596-018-0351-9

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  • DOI: https://doi.org/10.1007/s13596-018-0351-9

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