蓬莪术素 A 抑制 HepG2 肝癌细胞单层及三维培养中的增殖。

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

出版信息

Adv Exp Med Biol. 2020;1292:131-143. doi: 10.1007/5584_2020_523.

DOI:10.1007/5584_2020_523

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.

摘要

简介

药用植物在历史上一直被用于治疗疾病，特别是在亚洲部分地区。越南是一个热带国家，其森林中拥有种类繁多的植物，这些植物长期以来一直被用作治疗各种疾病的替代疗法。在这项研究中，我们旨在测试 Boesenbergia pandurata（B. pandurata）植物提取物衍生化合物（包括 Pinostropin、Pinocembrin、Alpinetin 和 Isopanduratin A）对 HepG2 肝癌细胞的生物活性。

方法

在这项研究中，使用了几种来自 Boesenbergia pandurata 植物提取物的化合物，包括 Pinostropin、Pinocembrin、Alpinetin 和 Isopanduratin A，以评估它们对 HepG2 肝癌细胞在单层培养条件（2D 培养）和三维培养条件（3D 培养）下的抗肿瘤作用；通过 Alamar Blue 测定法评估 HepG2 细胞的增殖。选择具有最强细胞毒性的化合物进行进一步分析，通过碘化丙啶（PI）染色法和 caspase 3/7 表达测定法进行分析。

结果

细胞毒性测定表明，Isopanduratin A 对在 2D 培养（IC50 为 357 ± 10 nM）和 3D 培养条件下生长的 HepG2 细胞具有最强的细胞毒性作用。对 HepG2 球体的 PI 染色表明，Isopanduratin A 对在球体（3D）中生长的 HepG2 细胞具有强大的细胞毒性，并破坏了球体的初始形状。在浓度为 500 nM 时，Isopanduratin A 在孵育 30 分钟后被证明能够诱导 caspase 3/7。

结论

本研究表明，从 B. pandurata 提取物中分离出的化合物 Isopanduratin A 对 2D 和 3D 培养条件下的细胞生长具有强烈的抑制作用。Isopanduratin A 还具有通过激活 caspase 3/7 在 HepG2 细胞中诱导细胞凋亡的能力。有必要进一步研究 Isopanduratin A 对 HepG2 细胞和其他癌细胞的诱导作用的机制。