Journal
ACTA PHARMACOLOGICA SINICA
Volume 33, Issue 2, Pages 242-249Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2011.152
Keywords
plumbagin; anticancer drug; TNF-alpha; cisplatin; gastric carcinoma; apoptosis; NF-kappa B
Funding
- National Natural Science Foundation of China [81072945, 81001670]
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Aim: To investigate the effects and underlying mechanisms of plumbagin, a naphthoquinone derived from medicinal plant Plumbago zeylanica, on human gastric cancer (GC) cells. Methods: Human gastric cancer cell lines SGC-7901, MKN-28, and AGS were used. The cell viability was examined using CCK-8 viability assay. Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay. Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry. Western blotting was used to assess the expression of both NF-kappa B-regulated gene products and TNF-alpha-induced activation of p65, I kappa B alpha, and IKK. The intracellular location of NF-kappa B p65 was detected using confocal microscopy. Results: Plumbagin (2.5-40 mu mol/L) concentration-dependently reduced the viability of the GC cells. The IC50 value of plumbagin in SGC-7901, MKN-28, and AGS cells was 19.12, 13.64, and 10.12 mu mol/L, respectively. The compound (5-20 mu mol/L) concentration-dependently induced apoptosis of SGC-7901 cells, and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNF-alpha and cisplatin. The compound (10 mu mol/L) downregulated the expression of NF-kappa B-regulated gene products, including IAP1, XIAP, Bcl-2, Bcl-xL, tumor factor (TF), and VEGF. In addition to inhibition of NF-kappa B p65 nuclear translocation, the compound also suppressed TNF-alpha-induced phosphorylation of p65 and IKK, and the degradation of I kappa B alpha. Conclusion: Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-kappa B pathway.
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