Visit our Expo - Redox and Inflammation signaling 2012

Session XVI : Chemopreventive agents Poster XVI, 7
Jaceosidin, a pharmacologically active flavone derived from Artemisia plants, induces
apoptosis in ras-transformed human breast epithelial (MCF10A-ras) cells
Min-Jung Kim1, Do-Hee Kim1, Ki Won Lee1, Do-Young Yoon2, and Young-Joon Surh1
1National Research Laboratory of Molecular Carcinogenisis & Chemoprevention,
College of Pharmacy, Seoul National University, Seoul 151-742 and 2Department of
Molecular Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
Extracts of Artemisia plants possess anti-inflammatory and anti-oxidative 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 induction
and NF-kB activation in mouse skin (H.J. Seo et al., Int. J. Cancer, 100: 456-62, 2002), and to
induce cell cycle arrest in ras-transformed human mammary epithelial (MCF10A-ras) cells
(D.H. Kim et al., Biochem Pharmacol., 68: 1081-7, 2004). In the present study, we examined
the ability of jaceosidin (4 ,5,7-trihydroxy-3 ,6-dimethoxyflavone) isolated from Artemisia
argyi to induce apoptosis in MCF10A-ras cells. Jaceosidin inhibited the growth of MCF10Aras
cells to a greater extent than eupatilin. Jaceosidin-induced apoptosis was mediated by
intracellular ROS accumulation in MCF10A-ras cells, which was blocked by the antioxidant
N-acetylcysteine (NAC). Jaceosidin has an additional hydroxyl moiety at the 4 -position
which was replaced by the methoxy group in eupatilin. To better assess the pro-apoptotic
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
decreased the ratio of pro-apoptotic Bax to the anti-apoptotic Bcl-2 and induced the cleavage
of caspase-3 and poly(ADP-ribose)polymerase (PARP). Moreover, jaceosidin elevated
expression of p53 and p21, while inhibited the activation of ERK1/2 which is an important
component of cell survival pathways. In conclusion, the pro-apoptotic activity of jaceosidin
is associated with ROS accumulation and inhibition of ERK1/2 activation in MCF10A-ras
cells.
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