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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anthocyanins / adverse effects
-
Anthocyanins / isolation & purification
-
Anthocyanins / pharmacology*
-
Anthocyanins / therapeutic use
-
Antineoplastic Agents, Phytogenic / adverse effects
-
Antineoplastic Agents, Phytogenic / isolation & purification
-
Antineoplastic Agents, Phytogenic / pharmacology*
-
Antineoplastic Agents, Phytogenic / therapeutic use
-
Carcinoma, Lewis Lung / prevention & control*
-
Carcinoma, Lewis Lung / secondary
-
Cell Adhesion / drug effects
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Cell Survival / drug effects
-
Dose-Response Relationship, Drug
-
Down-Regulation / drug effects*
-
Extracellular Signal-Regulated MAP Kinases / metabolism*
-
Glucosides / adverse effects
-
Glucosides / isolation & purification
-
Glucosides / pharmacology*
-
Glucosides / therapeutic use
-
Humans
-
Lung Neoplasms / drug therapy*
-
Lung Neoplasms / secondary
-
MAP Kinase Kinase 1 / genetics
-
MAP Kinase Kinase 1 / metabolism
-
Matrix Metalloproteinases, Secreted / genetics
-
Matrix Metalloproteinases, Secreted / metabolism
-
Mice
-
Neoplasm Transplantation
-
Oryza / chemistry
-
Phosphorylation / drug effects
-
RNA, Messenger / metabolism
-
Seeds / chemistry
-
Signal Transduction / drug effects*
-
Transcription Factor AP-1 / metabolism
-
Urokinase-Type Plasminogen Activator / genetics
-
Urokinase-Type Plasminogen Activator / metabolism
Substances
-
Anthocyanins
-
Antineoplastic Agents, Phytogenic
-
Glucosides
-
RNA, Messenger
-
Transcription Factor AP-1
-
peonidin 3-glucoside
-
Extracellular Signal-Regulated MAP Kinases
-
MAP Kinase Kinase 1
-
Urokinase-Type Plasminogen Activator
-
Matrix Metalloproteinases, Secreted