The results presented herein show that at clinically relevant concentrations (0–30 µM), the well-tolerated phytochemical berberine (BER) induces cell death in cultured human hepatocarcinoma (HepG2) cells as a model for liver cancer, primarily via apoptosis. Similar, relatively low-concentration single treatments using the structurally related phytochemical resveratrol (RSV), had little or no effect on cell viability but inhibited the cell cycle, while simultaneously increasing the strength of cellular adhesion. When used in combination, an RSV/BER cotreatment appeared to retain the ability of a single RSV treatment to increase cellular adhesion, but also induced a massive loss in hepatocarcinoma cellular viability, inducing cell death in more than 90% of cells. This model, therefore, suggests that it may be possible to use RSV to stabilise hepatocarcinomas against metastasis while using cotreatment with BER to simultaneously induce cell death. By measuring the changes in the activity of the pleiotropic enzyme transglutaminase 2 (TGM2), which is known to be overexpressed in hepatocarcinoma and many other tumours, we hypothesise a role for this enzyme in the activities of these two phytochemicals, and propose the potential use of this RSV/BER cotreatment as a chemotherapeutic in TGM2+ hepatocarcinomas.

中文翻译：

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一种以HePG2细胞系为模型治疗肝癌的新型白藜芦醇/小檗碱联合植物化学疗法

本文提供的结果表明，在临床相关浓度 (0–30 µM) 下，耐受性良好的植物化学小檗碱 (BER) 在作为肝癌模型的培养的人肝癌 (HepG2) 细胞中诱导细胞死亡，主要是通过细胞凋亡。类似的，使用结构相关的植物化学白藜芦醇 (RSV) 的相对低浓度单一处理对细胞活力几乎没有影响，但抑制了细胞周期，同时增加了细胞粘附的强度。当联合使用时，RSV/BER 联合治疗似乎保留了单一 RSV 治疗增加细胞粘附的能力，但也导致肝癌细胞活力的大量丧失，导致超过 90% 的细胞死亡。因此，该模型 表明有可能使用 RSV 来稳定肝癌以防止转移，同时使用与 BER 共同治疗同时诱导细胞死亡。通过测量已知在肝癌和许多其他肿瘤中过度表达的多效性转谷氨酰胺酶 2 (TGM2) 活性的变化，我们假设这种酶在这两种植物化学物质的活性中发挥作用，并提出潜在用途这种 RSV/BER 联合治疗作为 TGM2+ 肝癌的化疗药物。