Abstract
Purpose
Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model.
Methods
Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay.
Results
Pre-treatment of cells for 24 h with 2.5 μg/ml kavain and 5 μg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 μg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 μg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity.
Conclusion
This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.
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Availability of data and material
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the University of Melbourne—FA Kernot research grant. The authors would like to thank the staff at the National Herbarium of Victoria (MEL), including the digitizing officer Angharad Johnson and the manager of the herbarium specimen collection Pina Milne, who provided the image included in Fig. 1.
Funding
This study was supported by the University of Melbourne—FA Kernot research grant (2018 F.A. Kernot Early to Mid-career Research Grant).
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All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Research Ethics Committee of the University of Melbourne (No. 1340716.1).
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Yiannis, C., Huang, K., Tran, A.N. et al. Protective effect of kava constituents in an in vitro model of oral mucositis. J Cancer Res Clin Oncol 146, 1801–1811 (2020). https://doi.org/10.1007/s00432-020-03253-3
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DOI: https://doi.org/10.1007/s00432-020-03253-3