Tags

Type your tag names separated by a space and hit enter

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.
J Pharmacol Exp Ther. 2006 Aug; 318(2):484-94.JP

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.

Authors+Show Affiliations

Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16632641

Citation

Hsu, Ya-Ling, et al. "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." The Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 2, 2006, pp. 484-94.
Hsu YL, Cho CY, Kuo PL, et al. 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. J Pharmacol Exp Ther. 2006;318(2):484-94.
Hsu, Y. L., Cho, C. Y., Kuo, P. L., Huang, Y. T., & Lin, C. C. (2006). 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. The Journal of Pharmacology and Experimental Therapeutics, 318(2), 484-94.
Hsu YL, et al. 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. J Pharmacol Exp Ther. 2006;318(2):484-94. PubMed PMID: 16632641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hsu,Ya-Ling, AU - Cho,Chien-Yu, AU - Kuo,Po-Lin, AU - Huang,Yu-Ting, AU - Lin,Chun-Ching, Y1 - 2006/04/21/ PY - 2006/4/25/pubmed PY - 2006/9/1/medline PY - 2006/4/25/entrez SP - 484 EP - 94 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 318 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16632641/Plumbagin__5_hydroxy_2_methyl_14_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_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16632641 DB - PRIME DP - Unbound Medicine ER -