Anticancer mechanism of plumbagin, a natural compound, on non-small cell lung cancer cells.
BACKGROUND
Lung cancer is the leading cause of cancer-related deaths in the United States. Prevailing treatment options have limited therapeutic success in lung cancer, particularly non-small cell lung cancer (NSCLC), as it becomes resistant to therapy. Hence, better therapeutic options are immediately required for lung cancer. Plumbagin, a natural compound has been recently examined for its anticancer effect on different cancers.


METHODS
To determine the anticancer effect of plumbagin on NSCLC cell lines H460 and A549, cell viability, apoptotic, Western blot and reporter assays were performed.


RESULTS
Plumbagin significantly inhibited the growth of H460 cells compared to A549 cells, and down-regulated the expression of EGFR/Neu and its downstream signaling (Akt, NF-kappaB, Bcl-2 and survivin) in H460 cells. In addition, plumbagin up-regulated the expression of p53 and p21(CIP1/WAF1) causing cell cycle arrest in the G2/M-phase by down-regulating G2/M regulatory proteins (cyclinB1 and Cdc25B) in H460 cells. Furthermore, it activated the JNK/p38 signaling, leading to caspase-3 activation resulting in the induction of apoptosis.


CONCLUSIONS
Plumbagin exerted anticancer activity on NSCLC cells by modulating the pro-survival and pro-apoptotic signaling that causes induction of apoptosis.
Department of Clinical Sciences, College of Health Sciences, University of Kentucky, Lexington, KY 40536-0200, USA.
Rohini
R
Gomathinayagam
Srinivasan
S
Sowmyalakshmi
Firdaus
F
Mardhatillah
Raj
R
Kumar
Mohammad A
MA
Akbarsha
Chendil
C
Damodaran
D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009285:Naphthoquinones / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018797:Cell Cycle Proteins; D009285:Naphthoquinones; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C014758:plumbagin