title: Inhibition of B16F-10 melanoma-induced lung metastasis in C57BL/6 mice by Aerva lanata via induction of apoptosis.
abstract: In this study, the antimetastatic potential of the ethanolic extract of Aerva lanata was evaluated using the B16F-10 melanoma-induced lung metastasis model. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with A lanata inhibited tumor nodule formation in the lungs (70.53%), and there was a 65.3% increase in the survival rate of metastatic tumor-bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine, and uronic acid contents; serum sialic acid and γ-glutamyl transpeptidase levels; and histopathological analysis. In vitro studies using B16F-10 cells showed that A lanata inhibited migration of tumor cells, cell invasion through type-I collagen-coated polycarbonate filter and activation of matrix metalloproteinases. Treatment with A lanata induced apoptotic response, characterized by apoptotic morphology, a typical ladder of DNA fragmentation, and detection of 3' hydroxyl ends in DNA by TUNEL assay. There was an increase in the percentage of cells in the sub-G0/G1 phase indicating cell cycle arrest. A lanata treatment resulted in downregulation of bcl-2 and cyclin-D1 expression and upregulation of p53, bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were also found to be downregulated in A lanata-treated cells.
authors.affiliation: Amala Cancer Research Centre, Thrissur, Kerala, India.
authors.forename: Kodappully Sivaraman
authors.initials: KS
authors.lastname: Siveen
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D027703:Amaranthaceae / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D010936:Plant Extracts