Planta Med 2010; 76(3): 258-264
DOI: 10.1055/s-0029-1186083
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Sesquiterpene Lactone Parthenolide Markedly Enhances Sensitivity of Human A549 Cells to Low-Dose Oxaliplatin via Inhibition of NF-κB Activation and Induction of Apoptosis

Liang-Jie Fang1 [*] , Xue-Ting Shao2 [*] , Shuo Wang1 , Guo-Hua Lu1 , Tao Xu1 , Jian-Ying Zhou1
  • 1Department of Respiratory Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P. R. China
  • 2Department of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P. R. China
Further Information

Publication History

received March 20, 2009 revised August 2, 2009

accepted August 3, 2009

Publication Date:
11 September 2009 (online)

Preview

Abstract

Aberrant activation of NF-κB has been proposed as the major cause of chemoresistance in lung cancer. Low-dose chemotherapeutic agents with limited toxicity and achieving profoundly enhanced efficacy by blocking NF-κB activation may be a useful strategy in cancer therapy. Thus, this study was performed to explore the effect of parthenolide, a natural NF-κB inhibitor, on human lung cancer A549 cells treated with low-dose oxaliplatin, as well as to determine the potential mechanisms involved. We incubated A549 cells with different concentrations of parthenolide in the absence or presence of a low-dose of oxaliplatin for 48 h. Then, cell proliferation was determined by MTT assay, and flow cytometry was used to study apoptosis. PGE2 production in culture supernatants was detected by competitive ELISA, while expression of NF-κB/p65, COX-2, caspase-3 and caspase-9 proteins were analyzed by Western blot. Finally, compared to parthenolide or oxaliplatin alone, significant improvements in cell apoptosis and growth inhibition indexes were observed in the combined treatment. NF-κB/p65, COX-2, and PGE2 expression were suppressed by the co-application; meanwhile, caspase-3 and caspase-9 proteins were obviously activated. These findings indicate that parthenolide could markedly enhance sensitivity of A549 cells to low-dose oxaliplatin by inhibiting NF-κB activation and inducing apoptosis. Parthenolide in combination with a low dose of oxaliplatin may be a beneficial chemotherapeutic strategy for patients who cannot tolerate the severe side effects of the drug at therapeutic concentrations.

References

1 These authors contributed to this work equally.

Prof. Jian-Ying Zhou

Department of Respiratory Medicine
First Affiliated Hospital
School of Medicine
Zhejiang University

79 Qingchun Road

310009 Hangzhou

P. R. China

Phone: + 86 5 71 87 23 68 76

Fax: + 86 5 71 87 23 68 76

Email: Drzjy@163.com