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

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 imp...

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Main Authors: Samir Attoub, Kholoud Arafat, An Gélaude, Mahmood Ahmed Al Sultan, Marc Bracke, Peter Collin, Takashi Takahashi, Thomas E Adrian, Olivier De Wever
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3540099?pdf=render
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spelling doaj-eb65c067945f40de90e4a802d9276cdd2020-11-24T21:35:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5308710.1371/journal.pone.0053087Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.Samir AttoubKholoud ArafatAn GélaudeMahmood Ahmed Al SultanMarc BrackePeter CollinTakashi TakahashiThomas E AdrianOlivier De WeverA 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.http://europepmc.org/articles/PMC3540099?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Samir Attoub
Kholoud Arafat
An Gélaude
Mahmood Ahmed Al Sultan
Marc Bracke
Peter Collin
Takashi Takahashi
Thomas E Adrian
Olivier De Wever
spellingShingle Samir Attoub
Kholoud Arafat
An Gélaude
Mahmood Ahmed Al Sultan
Marc Bracke
Peter Collin
Takashi Takahashi
Thomas E Adrian
Olivier De Wever
Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
PLoS ONE
author_facet Samir Attoub
Kholoud Arafat
An Gélaude
Mahmood Ahmed Al Sultan
Marc Bracke
Peter Collin
Takashi Takahashi
Thomas E Adrian
Olivier De Wever
author_sort Samir Attoub
title Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
title_short Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
title_full Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
title_fullStr Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
title_full_unstemmed Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
title_sort frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description 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.
url http://europepmc.org/articles/PMC3540099?pdf=render
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