Targeting of Cancer Cell Drug Resistance Phenotype and Metastasis with Xanthium strumarium L. Extract

The antiproliferative activity of Xanthium strumarium L. extract (XFC), a traditional herbal medicine, is believed to alter the cell mitotic machinery, but the molecular mechanisms underlying its anticancer actions remain poorly characterized. We found that XFC exerted significant in vitro cell proliferation inhibitory effect against the ovarian, breast, and colon cancer cell line models tested. In vitro, XFC efficiently targeted both the cytotoxic drug chemoresistance phenotype of SKOV-3 and ES-2 ovarian cancer cells. Early apoptosis and late apoptosis were effectively induced by XFC extract in ES-2 cells, whereas late apoptosis and necrosis events were triggered in SKOV-3 cells. Cell cycling regulation was trapped by XFC extract in the G2/M phase in both the ES-2 and SKOV-3 cell models. This effect was, in part, attributable to increased dose-dependent tubulin polymerization, which was increased in SKOV-3 cells. Whereas XFC extract triggered poly (ADP-Ribose) polymerase (PARP) cleavage in both ES-2 and SKOV-3 cells, it only lowered Nrf2 in ES-2 cells and phosphorylated Akt levels in SKOV-3 cells. Interestingly, cell cycling regulators Cdk4, Cyclin D3, and p27 were all decreased in SKOV-3 cells. XFC extracts were effective in inhibiting in vitro migration in both ovarian cancer cell models. In addition, we found promising in vivo results when XFC exhibited significant antimetastatic action in a mouse model of colon cancer. Such in vitro and in vivo evidence confirm that XFC has excellent anti-tumor activity, and represents a potential promising source of anticancer agents in the targeting of the chemoresistance phenotype and of metastasis in human ovarian and colon cancers.