Jaceosidin Induces Apoptosis in ras-Transformed Human Breast Epithelial Cells through Generation of Reactive Oxygen Species

摘要

Extracts of Artemisia plants possess anti-inflammatory and antioxidative activities. Eupatilin (5,7-dihydroxy-3',4',6-tri-methoxy flavone), a pharmacologically active flavone derived from Artemisia asi atica, was shown to inhibit phorbol ester-induced cyclooxygenase-2 ex pression and NF-κB activation in mouse skin, and also to induce cell cycle arrest in ras-transformed human mammary epithelial (MCF10A-ras) cells. In this article, we examined the ability of jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) isolated from Artemisia argyi to in hibit the proliferation of MCF10A-ras cells. Jaceosidin reduced the viability of MCF10A-ras cells to a greater extent than eupatilin. Jaceo sidin treatment resulted in increased intracellular accumulation of re active oxygen species (ROS) in MCF10A-ras cells, which was blocked by the antioxidant N-acetylcysteine (NAC). NAC attenuated jaceosidin induced cytotoxicity. To better assess the proapoptotic effects of jaceo sidin, we analyzed the treated cells by the flow cytometry. MCF10A-ras cells treated with jaceosidin (100 μM) exhibited the increased proportion of hypodiploid or apoptotic cells (48.72% as composed to 7.78% in con trol cells). Jaceosidin treatment also increased the ratio of proapoptotic Bax to the antiapoptotic Bcl-2 and induced the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP). Moreover, jaceosidin elevated the expression of p53 and p21, while the compound inhibited the activation of ERK1/2 that is an important component of cell survival signaling.