Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf/MAPK/Erk pathway

// Minting Lin 1, * , Hong Bi 2, * , Yanyan Yan 3, * , Wenjing Huang 1 , Guiping Zhang 1 , Genshui Zhang 1 , Sili Tang 1 , Yun Liu 1 , Lingling Zhang 4 , Jinxiang Ma 5 , Jianye Zhang 1 1 School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China 2 Department of Pathology, Shanxi Provincial People’s Hospital, Taiyuan 030012, People’s Republic of China 3 Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Medical College, Shanxi Datong University, Datong 037009, People’s Republic of China 4 Pharmaceutical Department, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, People’s Republic of China 5 School of Public Health, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jianye Zhang, email: jianyez@163.com 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 ABSTRACT 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.