Exerts Anticancer Effect on Non–Small Cell Lung Cancer by Inhibiting Hedgehog Signaling via Suppression of TCTN3
| Autor: | Eunbi Jo MS, Hyun-Jin Jang MS, Lei Shen MS, Kyeong Eun Yang MS, Min Su Jang MS, Yang Hoon Huh PhD, Hwa-Seung Yoo PhD, Junsoo Park PhD, Ik Soon Jang PhD, Soo Jung Park PhD |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Integrative Cancer Therapies, Vol 19 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1534-7354 1552-695X 15347354 |
| DOI: | 10.1177/1534735420923756 |
| Popis: | This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of non–small cell lung cancer (NSCLC) cells and determine the underlying mechanisms. We performed a CCK-8 assay to detect cell proliferation, detection of morphological changes through transmission electron microscopy (TEM), annexin V–FITC/PI double staining to analyze apoptosis, and immunoblotting to measure the protein expression of apoptosis and hedgehog signaling–related proteins, with C militaris treated NSCLC cells. In this study, we first found that C militaris reduced the viability and induced morphological disruption in NSCLC cells. The gene expression profiles indicated a reprogramming pattern of genes and transcription factors associated with the action of TCTN3 on NSCLC cells. We also confirmed that the C militaris –induced inhibition of TCTN3 expression affected the hedgehog signaling pathway. Immunoblotting indicated that C militaris –mediated TCTN3 downregulation induced apoptosis in NSCLC cells, involved in the serial activation of caspases. Moreover, we demonstrated that the C militaris negatively modulated GLI1 transcriptional activity by suppressing SMO/PTCH1 signaling, which affects the intrinsic apoptotic pathway. When hedgehog binds to the PTCH1, SMO dissociates from PTCH1 inhibition at cilia. As a result, the active GLI1 translocates to the nucleus. C militaris clearly suppressed GLI1 nuclear translocation, leading to Bcl-2 and Bcl-xL down-regulation. These results suggested that C militaris induced NSCLC cell apoptosis, possibly through the downregulation of SMO/PTCH1 signaling and GLI1 activation via inhibition of TCTN3. Taken together, our findings provide new insights into the treatment of NSCLC using C militaris . |
| Databáze: | Directory of Open Access Journals |
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