Abstract | BACKGROUND AND AIMS: METHODS: RESULTS:
Plumbagin inhibited the growth of Panc-1 and Bxpc-3 cells in a dose-dependent and time-dependent manner. Liu's staining and transmission electron microscopy demonstrated morphological changes resembling apoptosis in Panc-1 cells treated with plumbagin. The degree of apoptosis was assessed by measuring the proportions of sub-G(1), annexin V+/ propidium iodide-, and terminal- deoxynucleotidyl-transferase-mediated-nick-end labeling (TUNEL)+ cells, and a significant increment in apoptotic cells was observed. Exposure to plumbagin caused the upregulation of Bax, a rapid decline in mitochondrial transmembrane potential, apoptosis-inducing factor overexpression in cytosol, and the cleavage of procaspase-9 and poly ADP-ribose polymerase. Activation of caspase-3, but not caspase-8, was evidenced by fluorometric substrate assay. Pretreatment with caspase inhibitors did not block plumbagin-induced apoptosis. Alternatively, it is possible that plumbagin downregulated phosphoinositide 3-kinase activity through a negative feedback mechanism. In an orthotopic pancreatic tumor model, plumbagin markedly inhibited the growth of Panc-1 xenografts without any significant effect on leukocyte counts or body weight. CONCLUSION:
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Authors | Chien-An Chen, Hen-Hong Chang, Chung-Yu Kao, Tung-Hu Tsai, Yu-Jen Chen |
Journal | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
(Pancreatology)
Vol. 9
Issue 6
Pg. 797-809
( 2009)
ISSN: 1424-3911 [Electronic] Switzerland |
PMID | 20110748
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2010 S. Karger AG, Basel. |
Chemical References |
- Antineoplastic Agents
- Naphthoquinones
- bcl-2-Associated X Protein
- Caspases
- plumbagin
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Topics |
- Animals
- Antineoplastic Agents
(isolation & purification, therapeutic use)
- Apoptosis
- Carcinoma
(drug therapy)
- Caspases
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Mice
- Mice, Nude
- Naphthoquinones
(isolation & purification, therapeutic use)
- Pancreatic Neoplasms
(drug therapy)
- Plumbaginaceae
(chemistry)
- Xenograft Model Antitumor Assays
- bcl-2-Associated X Protein
(analysis, metabolism)
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