Suppression of human ovarian SKOV-3 cancer cell growth by Duchesnea phenolic fraction is associated with cell cycle arrest and apoptosis

Objective. Duchesnea indica (Andr.) Focke has been commonly used to treat cancer in Asian countries of centuries, and more recently, has been shown to possess anticancer properties in vivo and in vitro. However, little is known about the underlying mechanism of its anticancer action. In the present study, we investigated the effect of Duchesnea phenolic fraction (DPF) on SKOV-3 ovarian cancer cells to provide insights into the mechanisms of growth suppression involved in DPF-mediated apoptosis and cell cycle arrest. Methods. Cytotoxic activity of DPF on SKOV-3 cells was determined using MTT assay, apoptosis (AO/EB staining, DNA fragmentation, FACS), caspase-3 activation and cell cycle analysis studies. The role of the molecules in apoptosis and cell cycle regulation was analyzed by Western blot and RT-PCR. Results. DPF significantly inhibited SKOV-3 cell proliferation in a dose-dependent manner and markedly induced apoptosis evidenced by characteristic apoptotic morphological changes, nuclear DNA fragmentation and sub-G1 peak. DPF suppressed Bcl-2 levels, enhanced Bax levels and Bax/Bcl-2 ratio, and simultaneously translocated Bax to mitochondria followed by mitochondrial release of cytochrome c into the cytosol and activation of effector caspase-3. Furthermore, DPF provoked S phase arrest in SKOV-3 cells with down-regulation of cyclin A, E, D1 and CDK2. Conclusion. DPF exhibits cytotoxicity towards human ovarian cancer SKOV-3 cells through induction of apoptosis via mitochondrial pathway and arresting cell cycle progression in S phase. All together, these data sustain our contention that DPF has anticancer properties and merits further investigation as a potential therapeutic agent. (c) 2007 Elsevier Inc. All rights reserved.