Inhibition of Metastasis of B16F-10 Melanoma Cells in C57BL/6 Mice by an Extract of Calendula Officinalis L Flowers

Abstract

Aim: To determine the effect of a Calendula officinalis flower extract on lung metastasis by B16F-10 melanomacells in C57BL/6 mice. Materials and <br/><b>Methods</b>: Male mice were injected with B16F-10 melanoma cells throughthe tail vein and simultaneously treated with C.officinalis flower extract. Parameters studied were lung tumornodule count, life span of animals, gamma glutamyl transpeptidase activity, sialic acid, TNF-α, IL-1β, IL-6, IL-2,GM-CSF, VEGF and TIMP-1 levels in serum, and lung hydroxyproline, uronic acid and hexosamine levels, aswell as histopathological features. Effects of C.officinalis on the expression of various genes involved in metastasislike matrix metalloproteases (MMPs), tissue inhibitor of metalloproteases (TIMPs), prolyl hydoxylase, lysyloxidase, nm23, and proinflammatory cytokines were also investigated. <br/><b>Results</b>: Simultaneous administrationof C.officinalis extract to tumor bearing C57BL/6 mice reduced the lung tumor nodules by 74% with 43.3%increase in life span. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-glutamyltranspeptidase in the metastatic controls were found to be significantly lowered in the C.officinalis treated animals.The extract also inhibited expression of MMP-2, MMP-9, prolyl hydroxylase and lysyl oxidase and activatedTIMP-1 and TIMP-2 and downregulated proinflammatory cytokines. <br/><b>Conclusions</b>: The present investigationindicated antimetastatic effects of Calendula officinalis flowers through the inhibition of key enzymes involvedin processes of metastasis.