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5 février 2012 7 05 /02 /février /2012 20:54
Acta Pharmacologica Sinica (2012) 33: 242–249; doi: 10.1038/aps.2011.152; published online 9 Jan 2012

Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

Jing Li1, Lin Shen1, Fu-rong Lu1, You Qin2, Rui Chen1, Jia Li3, Yan Li1, Han-zi Zhan5 and Yuan-qiao He4

1Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
3Department of Acupuncture & Moxibustion, Hubei University of Chinese Medicine, Wuhan 430065, China
4Department of Laboratory Animal Science, Nanchang University, Nanchang 330031, China
5University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Correspondence: Lin Shen, E-mail shenlinhb@yahoo.com.cn; Fu-rong Lu, furonglulove@163.com

Received 7 August 2011; Accepted 9 October 2011; Published online 9 January 2012.

Abstract
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-κB-regulated gene products and TNF-α-induced activation of p65, IκBα, and IKK. The intracellular location of NF-κB p65 was detected using confocal microscopy.
Results: Plumbagin (2.5–40 μmol/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 μmol/L, respectively. The compound (5–20 μmol/L) concentration-dependently induced apoptosis of SGC-7901 cells, and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNF-αand cisplatin. The compound (10 μmol/L) downregulated the expression of NF-κB-regulated gene products, including IAP1, XIAP, Bcl-2, Bcl-xL, tumor factor (TF), and VEGF. In addition to inhibition of NF-κB p65 nuclear translocation, the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK, and the degradation of IκBα.
Conclusion: Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-κB pathway.
Keywords: plumbagin; anticancer drug; TNF-α; cisplatin; gastric carcinoma; apoptosis; NF-κB

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