Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf/MAPK/Erk pathway
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Minting Lin1,*, Hong Bi2,*, Yanyan Yan3,*, Wenjing Huang1, Guiping Zhang1, Genshui Zhang1, Sili Tang1, Yun Liu1, Lingling Zhang4, Jinxiang Ma5, Jianye Zhang1
1School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China
2Department of Pathology, Shanxi Provincial People’s Hospital, Taiyuan 030012, People’s Republic of China
3Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Medical College, Shanxi Datong University, Datong 037009, People’s Republic of China
4Pharmaceutical Department, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, People’s Republic of China
5School of Public Health, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China
*These authors have contributed equally to this work
Jianye Zhang, email: [email protected]
Keywords: non-small cell lung cancer, parthenolide, B-Raf, MAPK/Erk pathway, c-Myc
Received: December 22, 2016 Accepted: February 12, 2017 Published: February 21, 2017
Non-small cell lung cancer (NSCLC), one type of lung cancer, owns high rates of morbidity and mortality. B-Raf is one of the promising oncogenic drivers of NSCLC. Parthenolide, a natural product, is mainly extracted from the herbal plant Tanacetum parthenium. The effect of parthenolide on NSCLC cells and its potential as B-Raf inhibitor were studied in this study. It’s shown that parthenolide exhibited the strong cytotoxicity against NSCLC cells with IC50 ranging from 6.07 ± 0.45 to 15.38 ± 1.13 μM. Parthenolide was also able to induce apoptosis, suppress proliferation and invasion in NSCLC cells. In terms of the involved mechanism, parthenolide suppressed GLC-82 cell response via targeting on B-Raf and inhibiting MAPK/Erk pathway signaling. The effect of parthenolide on B-Raf and MAPK/Erk pathway was further confirmed by RNA interference of B-Raf. Decreased expression of c-Myc in protein and mRNA level was also discovered, which is considered as the further downstream of the MAPK/Erk pathway. In addition, STAT3 activity inhibition by parthenolide contributed to its effect on GLC-82 cells, which is independent of PI3K pathway signaling and GSK3. All above provide an insight to understand the action of parthenolide as a potential B-Raf inhibitor in treatment of NSCLC.
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