title: Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts.
abstract: Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5 μM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5 μM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 μM at 24 h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100 μg/kg/dayi.p. for 24 days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer.
authors: Department of Pharmacology & Therapeutics, Faculty of Medicine & Health Sciences, UAE University, Al-Ain, PO Box: 17666, United Arab Emirates.
authors: Nadia
authors: N
authors: Al Marzouqi
authors: Rabah
authors: R
authors: Iratni
authors: Abderrahim
authors: A
authors: Nemmar
authors: Kholoud
authors: K
authors: Arafat
authors: Mahmood
authors: M
authors: Ahmed Al Sultan
authors: Javed
authors: J
authors: Yasin
authors: Peter
authors: P
authors: Collin
authors: Jan
authors: J
authors: Mester
authors: Thomas E
authors: TE
authors: Adrian
authors: Samir
authors: S
authors: Attoub
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006027:Glycosides / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology* / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D006027:Glycosides; D014315:Triterpenes; C534797:frondoside A