peonidin-3-glucoside and Carcinoma--Lewis-Lung

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.

Topics: Animals; Anthocyanins; Antineoplastic Agents, Phytogenic; Carcinoma, Lewis Lung; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Glucosides; Humans; Lung Neoplasms; MAP Kinase Kinase 1; Matrix Metalloproteinases, Secreted; Mice; Neoplasm Transplantation; Oryza; Phosphorylation; RNA, Messenger; Seeds; Signal Transduction; Transcription Factor AP-1; Urokinase-Type Plasminogen Activator

Dietary polyphenols, including anthocyanins, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, anticancer effects of peonidin 3-glucoside have not been clearly demonstrated, with only limited studies being available concerning the inhibitory effect of cyanidin 3-glucoside for tumor cell growth. Therefore, in this study, we have isolated and identified the two bioactive compounds, peonidin 3-glucoside and cyanidin 3-glucoside, from Oryza sativa L. indica, to treat various cancer cells. The results showed that, among analyzed cell lines, HS578T was the most sensitive to peonidin 3-glucoside and cyanidin 3-glucoside. Treatment with peonidin 3-glucoside or cyanidin 3-glucoside resulted in a strong inhibitory effect on cell growth via G2/M arrest. Regarding cell cyclerelated proteins, peonidin 3-glucoside treatment resulted in down-regulation of protein levels of cyclin-dependent kinase (CDK)-1, CDK-2, cyclin B1, and cyclin E, whereas cyanidin 3-glucoside could decrease the protein levels of CDK-1, CDK-2, cyclin B1, and cyclin D1. In addition, cyanidin 3-glucoside or peonidin 3-glucoside also induced caspase-3 activation, chromatin condensation, and cell death. Furthermore, anthocyanins from O. sativa L. indica were evidenced by their inhibition on the growth of Lewis lung carcinoma cells in vivo.

Topics: Animals; Anthocyanins; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Lewis Lung; Cell Cycle; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Glucosides; Humans; Male; Mice; Mice, Inbred C57BL; Neoplasms; Oryza; Time Factors