Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro

Antonio Celentano,Camile S Farah,Tami Yap,Pangzhen Zhang,Rita Paolini,Callisthenis Yiannis,Michael Mccullough,Nicola Cirillo

doi:10.1038/s41598-020-73058-4

Antonio Celentano, Camile S Farah + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-73058-4

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Abstract

Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity.Gas chromatography mass spectrometry (GCMS) was used to characterise the main constituents of two Kava preparations. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. Cell migration at 16 h was assessed using a Transwell migration assay. Cell invasion was measured at 22 h using a Matrigel assay. Cell adhesion was assessed at 90 min with a Cytoselect Adhesion assay. The two Kava preparations contained substantially different concentrations of the main chemical constituents. Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 μg/ml FKA, 2.5 μg/ml FKB and 10 μg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC.

Highlights

Kava is a beverage made from the ground roots of the plant Piper Methysticum
The two most researched constituents of Kava, Flavokawain A (FKA) and Flavokawain B (FKB), were present in both samples, with the commercial preparation from Vanuatu showing higher concentrations compared to traditional Fijian Kava (7.68 ± 0.83 vs 0.29 ± 0.21 g/Kg and 15.14 ± 1.05 vs 0.88 ± 0.01 g/Kg, respectively) (Table 1)
The constituents investigated in this study included 5 promising active compounds namely FKA, FKB, yangonin, methysticin and kavain

Summary

Introduction

Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. The same Kava constituents induced a significant reduction of OSCC cell migration and invasion. For the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. A recent systematic review published by our g roup[8] identified key chalcones, such as Flavokawain B (FKB), possessing the ability to induce apoptosis, inhibit proliferation, and interfere with metastasis within multiple cancer cells, in vitro and in vivo. Flavokawain A (FKA), a separate chalcone, was shown to induce cell cycle arrest and apoptosis in bladder and breast cancer c ells[14,15]

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