Journal ArticleDOI
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo
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TLDR
A critical role for JNK and p53 is suggested in plumbagin-induced G2/M arrest and apoptosis of human nonsmall cell lung cancer cells.Abstract:
This study first investigates the anticancer effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) in human nonsmall cell lung cancer cells, A549. Plumbagin has exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21 and reduced amounts of cyclinB1, Cdc2, and Cdc25C. Plumbagin treatment also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. Blockade of p53 activity by dominant-negative p53 transfection partially decreased plumbagin-induced apoptosis and G2/M arrest, suggesting it might be operated by p53-dependent and independent pathway. Plumbagin treatment triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss, cytochrome c release, and caspase-9 activation. We also found that c-Jun NH2-terminal kinase (JNK) is a critical mediator in plumbagin-induced cell growth inhibition. Activation of JNK by plumbagin phosphorylated p53 at serine 15, resulting in increased stability of p53 by decreasing p53 and MDM2 interaction. SP600125 (anthra [1,9-cd]pyrazol-6(2H)-one-1,9-pyrazoloanthrone), a specific inhibitor of JNK, significantly decreased apoptosis by inhibiting the phosphorylation of p53 (serine 15) and subsequently increased the interaction of p53 and MDM2. SP6000125 also inhibited the phosphorylation of Bcl-2 (Ser70) induced by plumbagin. Further investigation revealed that plumbagin's inhibition of cell growth effect was also evident in a nude mice model. Taken together, these results suggest a critical role for JNK and p53 in plumbagin-induced G2/M arrest and apoptosis of human nonsmall cell lung cancer cells.read more
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Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells
TL;DR: A critical role for AKT inhibition is implied in plumbagin-induced G2-M arrest and autophagy of human breast cancer cells, as well as survival signaling through the phosphatidylinositol 3-kinase/AKT signaling pathway.
Journal ArticleDOI
The Chemical Biology of Naphthoquinones and Its Environmental Implications
TL;DR: The chemistry, biochemistry, and cellular effects of 1,2- and 1,4-naphthoquinones and their derivatives are described, which are of particular interest because of their prevalence as natural products and as environmental chemicals.
Journal ArticleDOI
Perspectives on medicinal properties of plumbagin and its analogs
TL;DR: It has been suggested that designing “hybrid drug molecules” of plumbagin by combining it with other appropriate anticancer agents may lead to the generation of novel and potent anticancer drugs with pleiotropic action against human cancers.
Journal ArticleDOI
Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis.
TL;DR: The potential molecular targets and signaling pathways that mediate tumor onset and metastasis are discussed and some of the phytochemicals capable of targeting these signaling pathways which would make them potentially applicable to cancer chemoprevention, treatment and control of cancer progression are shed light.
Journal ArticleDOI
Noteworthy Secondary Metabolites Naphthoquinones – their Occurrence, Pharmacological Properties and Analysis
TL;DR: The utilizing of naphthoquinones for medicinal purposes and their occurrence in nature is reviewed and discussed and analytical techniques using for their analysis are reviewed.
References
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Journal ArticleDOI
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
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