Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf/MAPK/Erk pathway
Minting Lin1, Hong Bi2, Yanyan Yan3
1School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, 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.
Insights
Parthenolide, a natural compound, effectively combats non-small cell lung cancer (NSCLC) by inhibiting B-Raf and the MAPK/Erk pathway. This study highlights its potential as a novel therapeutic agent for NSCLC treatment.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Non-small cell lung cancer (NSCLC) presents significant morbidity and mortality.
- B-Raf mutations are key oncogenic drivers in NSCLC.
- Parthenolide, derived from Tanacetum parthenium, is explored for its anti-cancer properties.
Purpose of the Study:
- To investigate the anti-cancer effects of parthenolide on NSCLC cells.
- To evaluate parthenolide's potential as a B-Raf inhibitor.
- To elucidate the molecular mechanisms underlying parthenolide's action in NSCLC.
Main Methods:
- Cytotoxicity assays (IC50 determination) were performed on NSCLC cells.
- Apoptosis, proliferation, and invasion assays were conducted.
- Western blotting and RNA interference were used to analyze molecular pathways, including B-Raf, MAPK/Erk, c-Myc, and STAT3 signaling.
Main Results:
- Parthenolide demonstrated significant cytotoxicity against NSCLC cells (IC50: 6.07–15.38 μM).
- Parthenolide induced apoptosis and suppressed proliferation and invasion.
- Mechanistically, parthenolide inhibited B-Raf, suppressed the MAPK/Erk pathway, decreased c-Myc expression, and inhibited STAT3 activity.
Conclusions:
- Parthenolide exhibits potent anti-NSCLC activity through B-Raf inhibition and MAPK/Erk pathway suppression.
- Parthenolide's mechanism involves downregulation of c-Myc and STAT3 activity.
- Parthenolide represents a promising therapeutic candidate for NSCLC treatment, acting as a B-Raf inhibitor.
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