Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Sci Rep. 2020 Jun 19;10(1):9987. doi: 10.1038/s41598-020-66913-x.
Barringtonia racemosa leaf water extract (BLE) had been shown to have high gallic acid (GA) content and BLE has been postulated to have anti-proliferative effects towards colorectal cancer. This study aims to further investigate the mechanism underlying the anti-proliferative effect of BLE in Caco-2 cells and to determine if GA is responsible for the observed effects. Both BLE and GA inhibited Caco-2 cells in a dose-dependent manner. Cells exposed to IC concentration of BLE and GA showed reduced antioxidant activities. GA-treated Caco-2 cells experienced higher oxidative stress compared to cells treated with BLE. Both BLE and GA significantly up-regulated the expression of SLC2A1. BLE but not GA, significantly down-regulated the expression of ADH4. Meanwhile, GA but not BLE, significantly up-regulated AKRIB10 and GLO1 but significantly down-regulated HAGH. Alterations in gene expression were coupled with changes in extracellular glucose and pyruvate levels. While BLE decreased intracellular pyruvate, GA did the opposite. Both intracellular and extracellular D-lactate were not affected by either BLE or GA. GA showed more pronounced effects on apoptosis while BLE irreversibly reduced cell percentage in the G0/G1 phase. In conclusion, this study demonstrates the multiple-actions of BLE against Caco-2 cells, potentially involving various polyphenolic compounds, including GA.
瓶花木叶水提物（BLE）含有丰富的没食子酸（GA），并被推测对结直肠癌细胞具有抗增殖作用。本研究旨在进一步探讨 BLE 在 Caco-2 细胞中的抗增殖作用机制，并确定 GA 是否是导致观察到的效果的原因。BLE 和 GA 均以剂量依赖性方式抑制 Caco-2 细胞。暴露于 BLE 和 GA 的 IC 浓度的细胞显示抗氧化活性降低。与用 BLE 处理的细胞相比，GA 处理的 Caco-2 细胞经历更高的氧化应激。BLE 和 GA 均显著上调 SLC2A1 的表达。BLE 但不是 GA，显著下调 ADH4 的表达。同时，GA 但不是 BLE，显著上调 AKRIB10 和 GLO1，但显著下调 HAGH。基因表达的改变伴随着细胞外葡萄糖和丙酮酸水平的变化。虽然 BLE 降低了细胞内的丙酮酸，但 GA 则相反。细胞内和细胞外的 D-乳酸均不受 BLE 或 GA 的影响。GA 对细胞凋亡的影响更为显著，而 BLE 则不可逆地降低了 G0/G1 期的细胞百分比。总之，本研究表明 BLE 对 Caco-2 细胞具有多种作用，可能涉及多种多酚化合物，包括 GA。
