Format

Send to

Choose Destination
Oncotarget. 2017 Apr 4;8(14):23436-23447. doi: 10.18632/oncotarget.15584.

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

Author information

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.

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.

KEYWORDS:

B-Raf; MAPK/Erk pathway; c-Myc; non-small cell lung cancer; parthenolide

PMID:
28423582
PMCID:
PMC5410316
DOI:
10.18632/oncotarget.15584
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center