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

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

August 4, 2020 Medicine and Pharmacy 0

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.

Author(s) Details

Marbelis Francisco Fernandez,
Laboratoire d’Oncologie Moléculaire, Département de Chimie, Centre d’Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Université du Québec à Montréal, Montreal, Quebec, Canada.

Janet Piloto-Ferrer
Departamento de GeneticaToxicologica, Centro de Investigacion y Desarrollo de Medicamentos (CIDEM), Avenida 26, No. 1605 e/Puentes Grandes y Boyeros, La Habana, Cuba.

Borhane Annabi
Laboratoire d’Oncologie Moléculaire, Département de Chimie, Centre d’Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Université du Québec à Montréal, Montreal, Quebec, Canada.

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