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Published on: August 2, 2013
Artemether Attenuates the Progression of Non-small Cell Lung Cancer by Inducing Apoptosis, Cell Cycle Arrest and
Jian Chen1,2,3, Xiaofei Huang4, Cheng Tao1,2,3,5
1Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University.
Abstract:
Lung cancer is the most common cause of cancer death, approximately 85% of which are non-small cell lung cancer (NSCLC). Here we found that artemether (ART), a natural derivative of artemisinin, significantly inhibits the proliferation of NSCLC cells in a dose- and time-dependent manner. We also demonstrated that high concentration of ART induces apoptosis in NSCLC cells through down-regulating the level of anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2). While low concentration of ART inhibits the mRNA level of cell cycle related genes including cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 6 (CDK6), cyclin A2, cyclin B1 and cyclin D1, leading to cell cycle arrest in NSCLC cells. Moreover, we confirmed that low concentration of ART induces DNA double-stranded breaks (DSBs), as well as promoting cellular senescence in NSCLC cells by up-regulating the mRNA and protein level of p16. Taken together, ART represents a promising new anti-NSCLC drug candidate that could attenuate progression of NSCLC cells in a p53-independent manner through inducing apoptosis, cell cycle arrest and promoting cellular senescence.
Insights
Artemether (ART), a natural compound, effectively inhibits non-small cell lung cancer (NSCLC) cell growth. ART induces cancer cell death, halts cell cycle progression, and promotes senescence, showing potential as a novel anti-NSCLC therapeutic.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality.
- Artemisinin derivatives, like artemether (ART), are explored for their anti-cancer properties.
Purpose of the Study:
- To investigate the anti-proliferative effects of artemether (ART) on non-small cell lung cancer (NSCLC) cells.
- To elucidate the molecular mechanisms underlying ART's action in NSCLC.
Main Methods:
- Cell proliferation assays were performed on NSCLC cells treated with varying concentrations of ART.
- Apoptosis, cell cycle progression, DNA damage, and senescence markers were analyzed.
- Gene and protein expression levels of key regulatory molecules were quantified.
Main Results:
- ART significantly inhibited NSCLC cell proliferation in a dose- and time-dependent manner.
- High ART concentrations induced apoptosis by down-regulating Bcl-2, cIAP1, and cIAP2.
- Low ART concentrations caused cell cycle arrest by inhibiting cell cycle-related genes and induced DNA double-strand breaks and senescence via p16 upregulation.
Conclusions:
- Artemether (ART) exhibits potent anti-NSCLC activity through multiple mechanisms.
- ART induces apoptosis, cell cycle arrest, and cellular senescence in NSCLC cells.
- ART represents a promising therapeutic candidate for NSCLC, acting independently of p53.
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