Anthocyanin Inhibition of Carcinoma Invasion-Two Mechanisms in Human Lung Carcinoma

Abstract

Metastasis, the major cause of cancer death, is a multi-step process involving cell adhesion and proteolytic degradation of the ECM (extracellular matrix), essential to achieving cell motility. Many bioactive properties of anthocyanins, present in various fruits and vegetables as natural colorants, have been well characterized. They are widely used for their antioxidant properties. Recent studies have also revealed pleiotropic anticancer and antiproliferative capabilities of anthocyanins. Berry extract contains high amounts of anthocyanins and is commonly used in certain diet and therapeutic applications. This study demonstrates that, in the absence of cytotoxicity, anthocyanins from both roselle (HAs, extracted from Hibiscus sabdariffa L., a local Soft drink material and medical herb possessing antioxidant activity) and mulberry (MACs, extracted from Morus alba L.) exerted a dose- and time-dependent inhibitory effect on the invasion, motility, and adhesion of highly metastatic A549 human lung carcinoma cells. We examined the effect of HAs and MACs on factors of cancer metastasis. We treated A549 cells with various concentrations of HAs and MACs (up to 1 mg/mL), for set periods, then subjected cells to gelatin zymography and casein zymography to investigate the expression of matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (u-PA). Treatment by both anthocyanin preparations was found to decrease the expression of MMP-2 and u-PA in a concentration- and time-dependent manner. Both preparations also limited cell motility and cell-matrix adhesion. Together, these results suggest that anthocyanins may act to decrease the in vitro invasiveness of cancer cells and therefore, reduce the invasion and metastasis of tumor cells. This study suggests a possible role for anthocyanins in cancer therapy.