Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts

Nadia Al Marzouqi, Rabah Iratni, Abderrahim Nemmar, Kholoud Arafat, Mahmood Ahmed Al Sultan, Javed Yasin, Peter Collin, Jan Mester, Thomas E. Adrian, Samir Attoub

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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 24 h. 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/day i.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.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalEuropean Journal of Pharmacology
Volume668
Issue number1-2
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • Apoptosis
  • Breast cancer
  • Caspases
  • Frondoside A
  • Invasion
  • Tumor growth

ASJC Scopus subject areas

  • Pharmacology

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