Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis

PLoS One. 2013;8(1):e53087. doi: 10.1371/journal.pone.0053087. Epub 2013 Jan 8.

Abstract

A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Glycosides / pharmacology
  • Glycosides / therapeutic use*
  • Humans
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control*
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / prevention & control*
  • Neovascularization, Pathologic / drug therapy*
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*

Substances

  • Antineoplastic Agents, Phytogenic
  • Glycosides
  • Triterpenes
  • frondoside A
  • Caspases

Grant support

This work was financially supported by the FMHS grant number NP/08/27 (SA), the UAE University grant under a contract no. 01-04-8-11/09 (SA), the Terry Fox Fund for Cancer Research (SA and TA), the UAEU-NRF 09/10 grant number 21MO72 (SA), and the Maine Technology Institute, Gardiner, Maine, USA, and the National Cancer Institute, RAPID Program (PC). The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.