Isopanduratin A Isolated from Boesenbergia pandurata Reduces HepG2 Hepatocellular Carcinoma Cell Proliferation in Both Monolayer and Three-Dimensional Cultures

Abstract

Introduction: Medicinal plants have been used for disease treatment throughout history, especially in parts of Asia. Vietnam is a tropical country which possesses forests with a wide diversity of plants, which have a long history of being used as alternative remedies for treatment of various diseases. In this study, we aimed to test the bioactivity of Boesenbergia pandurata (B. pandurata) plant extract-derived compounds, including Pinostropin, Pinocembrin, Alpinetin, and Isopanduratin A, on HepG2 hepatocellular carcinoma cells.

Method: In this study, several compounds from Boesenbergia pandurata plant extract, including Pinostropin, Pinocembrin, Alpinetin, and Isopanduratin A, were used to evaluate their antitumor effects on HepG2 hepatocellular carcinoma cells in both monolayer culture condition (2D culture) and three-dimensional culture condition (3D culture); HepG2 cell proliferation was assessed by Alamar Blue assay. The compound which had the strongest cytotoxicity was selected for further analysis by Propidium Iodide (PI) staining assay and caspase 3/7 expression assay.

Results: The cytotoxicity assay showed that Isopanduratin A had the strongest cytotoxic effect on HepG2 cells grown in both 2D culture (IC50 at 357 ± 10 nM) and 3D culture conditions (IC50 at 744 ± 18 nM). The PI staining of HepG2 spheroids demonstrated that Isopanduratin A was potently cytotoxic to HepG2 cells growing in spheroids (3D) and destroyed the initial shape of the spheroids. Isopanduratin A was shown to induce caspase 3/7 after 30 min of incubation at the concentration of 500 nM.

Conclusion: This study demonstrated that the compound Isopanduratin A isolated from B. pandurata extract has a strong inhibitory effect on cell growth in 2D and 3D culture conditions. Isopanduratin A also has the ability to induce apoptosis in HepG2 cells via activation of caspase 3/7. Further investigations on the mechanisms of Isopanduratin A-induced effects on HepG2 cells, and other cancer cells, are necessary.

Keywords: Antitumor activity; Boesenbergia pandurata; Hepatocellular carcinoma; Ngai Bun.