Poster Presenter
Frondoside A Inhibits Human Breast
Cancer Cell Survival, Invasion And The Growth Of Breast Tumor Xenografts
In Athymic Mice
Al Marzouqi Y.N; Iratni R; Arafat K; Gaben A.M; Mester J;
Al Sultan M.A.H; Nemmar A; Woodward C, Collin P; Gespach C; Adrian
TE and Attoub S.
UAE
Breast cancer is a major challenge for pharmacologist to develop
new compounds/drugs in order to improve the survival and quality
of life of cancer patients. More that 1.5 million new cases of breast
cancers are estimated to be diagnosed in 2010, with 1 million deaths
each year. Over recent years, a growing interest in natural compounds
with anti-cancer potential encouraged further pre-clinical screening
programs for these drugs in vitro and in vivo. Natural compounds
with potential clinical application have been isolated from marine
plants and animals. Frondoside A is a triterpenoid glycoside isolated
from the Atlantic sea cucumber, Cucumaria frondosa. A recent study
demonstrated that low concentration of Frondoside A inhibited growth
of human pancreatic cancer cells.
In this study, we investigated the
impact of Frondoside A on human breast cancer cell survival and
invasion in vitro, on tumour growth and metastasis in nude
mice, using the human breast cancer cell lines MCF7, MDA-MB-231,
and the highly metastatic subline MDA-MB-231-1833. The non-tumorigenic
MCF10-A cell line derived from normal human mammary epithelium was
used as control. Frondoside A (0.01-5 µM) selectively decreased
the viability of breast cancer cells in a concentration and time
dependent manner. Of note, MCF10-A cells were shown to be resistant
to this cytotoxic effect of Frondoside A. In breast cancer cells,
Frondoside A effectively increased the sub-G1 fraction of apoptotic
cells through the activation of p53, and subsequently the caspases
9 and 3/7 cell death pathways. The impact of Frondoside A on cancer
cell motility and invasion was investigated using wound healing
and Matrigel invasion assays. Frondoside A induces a concentration
dependent inhibition of MDA-MB-231 cell motility and invasion. Interestingly,
Frondoside A strongly decreased the growth of MDA-MB-231 tumor xenografts
after intra-peritoneal injection (µg/kg/day) in athymic mice.
Taken together, these findings identify Frondoside A as a promising
novel breast anticancer agent with potentially very limited toxicity
on cancer patients.
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