Plumbagin activates ERK1/2 and Akt via superoxide, Src and PI3-kinase in 3T3-L1 Cells

Yang, Sen; Chang, Shi-Chuan; Wen, Hao; Ching-Yu, Chen; Liao, Junyi; Chang, Chung-Ho

doi:10.1016/j.ejphar.2010.04.016

Cited by 26 publications

(26 citation statements)

References 41 publications

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“…Recent studies suggest that ERK regulates the maturation of autophagic vacuoles. ERK is associated with the formation of large cytoplasmic vacuoles (42). ERK is reported here to be activated in response to SU11274 for the induction of autophagy.…”

Section: Discussionmentioning

confidence: 98%

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Liu

Yang

et al. 2012

J Pharmacol Sci

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Abstract. SU11274, a small molecule inhibitor of c-Met, was reported to induce apoptosis in human non-small-cell lung cancer (NSCLC) cells. However, SU11274-mediated autophagy in NSCLC cells has rarely been reported. The aim of this study was to elucidate the molecular mechanisms mediating SU11274-induced autophagy in NSCLC A549 cells. Here we reported that SU11274-induced autophagy was accompanied with an increase in the conversion of LC3-I to LC3-II and up-regulation of Beclin-1 expression. Subsequently, we also found that small interfering RNA against c-Met induced A549 cell autophagy while promotion of c-Met by hepatocyte growth factor (HGF) suppressed A549 cell autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed SU11274-induced cell death, suggesting that SU11274-induced autophagy caused cell death. Further study showed that ERK and p53 were activated after SU11274 treatment. Interruption of ERK and p53 activities decreased SU11274-induced autophagy, and blocking of ERK by the specific inhibitor PD98059 suppressed SU11274-induced p53 activation. Moreover, ERK activation upregulated Beclin-1 expression through induction of Bcl-2 phosphorylation, but p53 did not induce Bcl-2 phosphorylation. In conclusion, inhibition of c-Met induced autophagic cell death, which was associated with ERK-p53 activation and ERK-mediated Bcl-2 phosphorylation in A549 cells.

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Section: Discussionmentioning

confidence: 98%

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Liu

Yang

et al. 2012

J Pharmacol Sci

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“…Endostatin stimulated superoxide production through the increase of intracellular ceramide levels in bovine coronary arterial endothelium (Zhang et al, 2005). Yang et al (2010) reported that Plumbagin activated PI3K/Akt pathway through the superoxide generation in 3T3-L1 cells. This study demonstrated that NAC, an antioxidant, inhibited endostatin-induced Akt phosphorylation.…”

Section: Discussionmentioning

confidence: 98%

Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway

Okada

Oba

Yamawaki

2015

European Journal of Pharmacology

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“…Previous studies have demonstrated that PL exhibits anti-Haemonchus contortus (7), anti-bacterial (8), hypolipidaemic and anti-atherosclerotic (9), anti-inflammation (10) and anticancer effects (11,12). The molecular mechanisms of the anticancer effects of PL include inactivition of NF-κB and Bcl-2 (13,14), disruption of the microtubule network (15), breakage of DNA (16), generation of reactive oxygen species (17,18) and cell cycle arrest (19,21). PL was also found to improve the radiation effect in the treatment of mouse tumor xenograft models (22,23).…”

Section: Introductionmentioning

confidence: 99%

Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells

et al. 2011

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Abstract. Osteosarcoma, which is the most common primary bone tumor, occurs most frequently in adolescents. A number of studies have indicated that plumbagin (PL) (5-hydroxy-2-methyl-1, 4-naphthoquinone), a compound found in the plants of the Plumbaginaceae and Droseraceae families, possesses anticancer activity. However, its anticancer effects and mechanisms against osteosarcoma have not been explored. To determine the anticancer effect of PL on osteosarcoma cell lines MG-63 and U2OS, cell viability, apoptosis, cell cycle distribution, caspase-3 and caspase-9 activity and intracellular reactive oxygen species (ROS) generation were measured, and Western blot analyses were performed. PL significantly inhibited the growth of osteosarcoma cells, particularly U2OS cells. PL up-regulated the expression of p53 in U2OS cells and p21 in the two osteosarcoma cell lines causing cell cycle arrest by decreasing the expression of murine double minute 2 (MDM2)/ cyclin B1 and cyclin D1. Furthermore, PL altered the ratio of Bax/Bcl-2, and may have triggered the mitochondrial apoptotic pathway, resulting in caspase-3 and caspase-9 activation. We also found that PL induced the generation of ROS in osteosarcoma cell lines. To conclude, PL exerted anticancer activity on osteosarcoma cells by inducing pro-apoptotic signaling and modulating the intracellular ROS that causes induction of apoptosis. These effects may relate to the p53 status.

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Plumbagin activates ERK1/2 and Akt via superoxide, Src and PI3-kinase in 3T3-L1 Cells

Cited by 26 publications

References 41 publications

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway

Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells

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