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.

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These results may further the understanding of ROS-RE and aPKC in the control of PPA anorexia.

. Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats. Am J Physiol Endocrinol Metab 292: E123-E131, 2007. First published August 8, 2006; doi:10.1152/ajpendo.00195.2006.-Although amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter abundant in the brain, molecular mechanisms underlying this effect are not well known. This study examined the possible role of protein kinase A (PKA) and cAMP response element-binding protein (CREB) signaling in this anorectic effect, and the results showed that both PKA and CREB mRNA levels in hypothalamus were increased following AMPH treatment, which was relevant to a reduction of NPY mRNA level. To determine whether PKA or CREB was involved in the anorectic response, intracerebroventricular infusions of antisense oligonucleotide (or missense control) were performed 60 min before daily AMPH treatment in conscious rats, and results showed that either PKA or CREB knockdown could block AMPH-induced anorexia as well as restore NPY mRNA level, indicating the respective involvement of PKA and CREB signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA and CREB signaling may involve the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression. amphetamine; neuropeptide Y; feeding behavior; signaling transduction AMPHETAMINE (AMPH) is a well-known appetite suppressant. After the approval in the 1940s and 1950s of AMPH and AMPH-like compounds for the treatment of obesity, AMPH has served as a prototype for the development of subsequent anorectic drugs such as phentermine and phenylpropanolamine (11,38). AMPH derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, Adam), have emerged over the last two decades as common recreational psychostimulants or "club drugs" because of their hallucinogenic effect with relatively low toxicity (51). In humans, AMPH can be used to treat attention-deficit/hyperactivity disorder (ADHD) because of its psychomotor effects, such as increased attention, restlessness, and feelings of confidence (5, 6). Because of these effects of AMPH, the mechanisms behind AMPH-induced anorexia, weight loss, and psychomotor effects have been investigated extensively.AMPH is regarded as an indirect dopamine agonist. The anorectic action of AMPH is relevant to the central release of biogenic amines (33, 53) that in turn may lead to an inhibitory action on hypothalamic neuropeptide Y (NPY) (28). Acute treatment with AMPH markedly decreases food intake, followed by a gradual return of normal food intake with subsequent daily treatment (27,30,46). NPY, an orexigenic neurotransmitter in the brain, appears to play an essential role in the regulation of feeding behavior (7, 61) and is postulated to control the energy balance by stimulating feeding behavior and inhibiting th...