Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
Chem Biol Interact. 2011 Sep 5;193(2):180-9. doi: 10.1016/j.cbi.2011.06.009. Epub 2011 Jul 3.
Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism underlying its action is not completely understood. Here, we evaluated the effects of apigenin on the levels of expression and activity of antioxidant enzymes, and the involvement of ROS in the mechanism of cell death induced by apigenin in HepG2 human hepatoma cells. Upon treatment with apigenin, HepG2 cells displayed a reduction in cell viability in a dose- and time-dependent manner, and some morphological changes. In addition, apigenin treatment induced ROS generation and significantly decreased the mRNA levels and activity of catalase and levels of intracellular GSH. On the other hand, apigenin treatment did not alter the expression or activity levels of other antioxidant enzymes. Addition of exogenous catalase significantly reduced the effects of apigenin on HepG2 cell death. We also demonstrated that HepG2 cells are more sensitive to apigenin-mediated cell death than are primary cultures of mouse hepatocytes, suggesting a differential toxic effect of this agent in tumor cells. Our results suggest that apigenin-induced apoptosis in HepG2 cells may be mediated by a H(2)O(2)-dependent pathway via reduction of the antioxidant defenses.
芹菜素已被报道能抑制癌细胞增殖；然而，其作用机制尚不完全清楚。在这里，我们评估了芹菜素对 HepG2 人肝癌细胞中抗氧化酶表达和活性水平的影响，以及 ROS 在芹菜素诱导细胞死亡机制中的作用。用芹菜素处理 HepG2 细胞后，细胞活力呈剂量和时间依赖性下降，并出现一些形态变化。此外，芹菜素处理诱导 ROS 生成，并显著降低过氧化氢酶的 mRNA 水平和活性以及细胞内 GSH 水平。另一方面，芹菜素处理并不改变其他抗氧化酶的表达或活性水平。外源性过氧化氢酶的添加显著降低了芹菜素对 HepG2 细胞死亡的影响。我们还表明，与小鼠原代肝细胞培养物相比，HepG2 细胞对芹菜素介导的细胞死亡更为敏感，这表明该药物在肿瘤细胞中具有不同的毒性作用。我们的结果表明，芹菜素诱导的 HepG2 细胞凋亡可能是通过降低抗氧化防御来介导 H2O2 依赖性途径。
