Antimetastatic potential of vernolide-A, a sesquiterpenoid from Vernonia cinerea L.

Abstract

The inhibitory effect of vernolide-A (C(21)H(28)O(7)) on lung metastasis induced by B16F-10 melanoma cells was studied using C57BL/6 mice. Vernolide-A was administered in three different modalities such as simultaneously with tumor, prophylactic to tumor and after tumor development. Maximum inhibition in the metastasis was observed when vernolide-A was administered simultaneously with tumor. There was 89.39% inhibition of lung tumor nodule formation and 88.51% increase in the life span of metastatic tumor-bearing animals. Highly elevated levels of lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid, serum γ-glutamyl transpeptidase (GGT) and serum vascular endothelial growth factor (VEGF) in the metastatic control animals were found to be significantly lowered in the vernolide-A-treated animals. Histopathological analysis of lung tissues also correlated with these results. Vernolide-A administration downregulated the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, extracellular-signal-regulated kinase-1 (ERK-1), ERK-2 and VEGF in the lung tissue of B16F-10 melanoma challenged animals. In the in vitro system, vernolide-A showed a significant inhibition of invasion of B16F-10 melanoma cells across the collagen matrix. Vernolide-A treatment also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. Vernolide-A could inhibit MMP-2 and MMP-9 protein expression in gelatin zymographic analysis of B16F-10 cells. (3)H-thymidine proliferation assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro. These results indicate that vernolide-A could inhibit the metastatic progression of B16F-10 melanoma cells in mice.

• Authors: P Pratheeshkumar, Girija Kuttan
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 31 Issue 1 Pg. 66-80 (Jan 2012) ISSN: 1477-0903 [Electronic] England
• PMID: 21708884 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts
• Sesquiterpenes
• Uronic Acids
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• vernolide-A
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse
• N-Acetylneuraminic Acid
• Hydroxyproline

Topics

• Animals
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hydroxyproline (metabolism)
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology, secondary)
• Male
• Matrix Metalloproteinase 2 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Melanoma, Experimental (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• N-Acetylneuraminic Acid (blood)
• Neoplasm Invasiveness
• Phytotherapy
• Plant Extracts (chemistry)
• Sesquiterpenes (isolation & purification, pharmacology, therapeutic use)
• Uronic Acids (metabolism)
• Vascular Endothelial Growth Factor A (blood, genetics)
• Vernonia (chemistry)