Peonidin 3-Glucoside Inhibits Lung Cancer Metastasis by Downregulation of Proteinases Activities and MAPK Pathway

Abstract

Anthocyanins, present in various vegetables and fruits as a nature colorant, have broad activities including anticarcinogenesis and antimutagenesis, which are generally attributed to their antioxidant activities. However, limited studies have been available concerning the inhibitory effect of peonidin 3-glucoside (P3G) for cancer metastasis. Here, we demonstrated that P3G could significantly inhibit the invasion (P < 0.001), motility (P < 0.05), secretion of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) of lung cancer cells. Meanwhile, P3G attenuated phosphorylation of extracellular signal-regulated kinase (ERK)1/2, a member of mitogen-activated protein kinase (MAPK) family involved in the upregulation of MMPs and u-PA, and also inhibited the activation of activating protein-1 (AP-1) as shown by Western blot and electrophoretic mobility shift assay. Thus, the inhibitory effects of P3G may be at least partly through inactivation of ERK 1/2 and AP-1 signaling pathways as confirmed by abolishment of P3G-inhibited H1299 cell invasion by overexpression of MAPK kinase 1 (MEK1). Finally, P3G was evidenced by its inhibition on the metastasis of Lewis lung carcinoma cells in vivo (P < 0.001). Taken together, these findings suggested that P3G could reduce the metastasis of lung cancer cells, thereby constituting an adjuvant treatment for metastasis control.

ACKNOWLEDGMENTS

This study was supported by grants of National Science Council, Republic of China (NSC 96–2313-B-166–002-MY2 and NSC 96–2311-B-040–005-MY2). Mao-Lin Ho and Pei-Ni Chen contributed equally as first author.