Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway.
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.
Ho
Mao-Lin
ML
Institute of Medicine, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Chen
Pei-Ni
PN
Chu
Shu-Chen
SC
Kuo
Dong-Yih
DY
Kuo
Wu-Hsien
WH
Chen
Jia-Yuh
JY
Hsieh
Yih-Shou
YS
D000818:Animals; D000872:Anthocyanins / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000517:prevention & control* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005960:Glucosides / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D012275:Oryza / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D000872:Anthocyanins; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C480521:peonidin 3-glucoside; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D014568:Urokinase-Type Plasminogen Activator; D053505:Matrix Metalloproteinases, Secreted