Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer
| العنوان: | Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer |
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| المؤلفون: | Alexander T.H. Wu, Tai Shan Cheng, Jing Ming Chen, Tse-Hung Huang, Jade H.M. Hsu, Yun Hsuan Yang, Yu Chen Tsai, Thu Ha Tran, Jin Mei Lai, Chi Ying F. Huang, Yeh Shiu Chu, Peter Mu Hsin Chang, Yu-Lun Kuo |
| المصدر: | Cancers Volume 11 Issue 7 Cancers, Vol 11, Iss 7, p 1003 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, withaferin A, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, synergistic effect, medicine, Epidermal growth factor receptor, Lung cancer, PI3K/AKT/mTOR pathway, Cisplatin, biology, business.industry, Cancer, respiratory system, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, respiratory tract diseases, 030104 developmental biology, Pemetrexed, Oncology, chemistry, non-small-cell lung cancer, Apoptosis, Withaferin A, 030220 oncology & carcinogenesis, Cancer research, biology.protein, business, connectivity map, medicine.drug |
| الوصف: | Low response rate and recurrence are common issues in lung cancer thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti&ndash lung cancer and anti&ndash lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::662fddeb9cb680567b9a18c8672f0694Test https://pubmed.ncbi.nlm.nih.gov/31319622Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....662fddeb9cb680567b9a18c8672f0694 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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