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Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis
Samir Attoub1, Kholoud Arafat, An Gélaude
1Department of Pharmacology & Therapeutics, Faculty of Medicine & Health Sciences, U. A. E. University, Al-Ain, United Arab Emirates. samir.attoub@uaeu.ac.ae
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.
Insights
Frondoside A, a compound from sea cucumbers, shows promise in fighting lung cancer. It effectively reduced cancer cell viability, migration, and tumor growth in preclinical studies with minimal toxicity.
Area of Science:
- Pharmacology
- Oncology
- Marine Natural Products
Background:
- Developing less toxic lung cancer therapeutics is crucial for improving patient survival.
- Frondoside A, a triterpenoid glycoside from Cucumaria frondosa, is a safe compound with potential anti-cancer properties.
Purpose of the Study:
- To investigate the efficacy of Frondoside A against lung cancer.
- To evaluate its effects on cancer cell survival, migration, invasion, tumor growth, metastasis, and angiogenesis, both alone and with cisplatin.
Main Methods:
- In vitro studies on various cancer cell lines (LNM35, A549, etc.) to assess viability, migration, and invasion.
- In vivo studies using LNM35 tumor xenografts in athymic mice to evaluate tumor growth, metastasis, and angiogenesis.
- Chick Chorioallantoic Membrane (CAM) assay for angiogenesis inhibition.
- Combination therapy with cisplatin.
Main Results:
- Frondoside A induced dose-dependent cancer cell death via caspase 3/7 pathway (IC50: 1.7-2.5 µM).
- It inhibited cell migration, invasion, and angiogenesis in vitro.
- In vivo, Frondoside A reduced tumor growth, angiogenesis, and lymph node metastasis without significant toxicity.
- It enhanced cisplatin's anti-tumor effects.
Conclusions:
- Frondoside A demonstrates significant anti-cancer activity against lung cancer models.
- It possesses anti-migratory, anti-invasive, and anti-angiogenic properties.
- Frondoside A is a promising therapeutic candidate for lung cancer, potentially in combination with chemotherapy.
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