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

Abstract

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 asiatica, was shown to inhibit phorbol ester‐induced cyclooxygenase‐2 expression 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 inhibit the proliferation of MCF10A‐ras cells. Jaceosidin reduced the viability of MCF10A‐ras cells to a greater extent than eupatilin. Jaceosidin treatment resulted in increased intracellular accumulation of reactive 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 jaceosidin, 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 control 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.