دورية أكاديمية
12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway
العنوان: | 12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway |
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المؤلفون: | Ju-Ying Tsai, Dóra Rédei, Judit Hohmann, Chin-Chung Wu |
المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 20, p 7579 (2020) |
بيانات النشر: | MDPI AG, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | prostratin, phorbol ester, PKC-δ, PKD, ERK, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Prostratin, a non-tumor promoting 12-deoxyphorbol ester, has been reported as a protein kinase C (PKC) activator and is shown to have anti-proliferative activity in certain cancer cell types. Here we show that GRC-2, a prostratin analogue isolated from Euphorbia grandicornis, is ten-fold more potent than prostratin for inhibiting the growth of human non-small cell lung cancer (NSCLC) A549 cells. Flow cytometry assay revealed that GRC-2 and prostratin inhibited cell cycle progression at the G2/M phase and induced apoptosis. The cytotoxic effect of GRC-2 and prostratin was accompanied by activation and nuclear translocation of PKC-δ and PKD as well as hyperactivation of extracellular signal-related kinase (ERK). Knockdown of either PKC-δ, PKD or ERK significantly protected A549 cancer cells from GRC-2- and prostratin-induced growth arrest as well as apoptosis. Taken together, our results have shown that prostratin and a more potent analogue GRC-2 reduce cell viability in NSCLC A549 cells, at least in part, through activation of the PKC-δ/PKD/ERK pathway, suggesting the potential of prostratin and GRC-2 as anticancer agents. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/21/20/7579; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms21207579 |
URL الوصول: | https://doaj.org/article/ba6e2ff09ee444f88c2201f5ce7e3d7d |
رقم الأكسشن: | edsdoj.ba6e2ff09ee444f88c2201f5ce7e3d7d |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
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DOI: | 10.3390/ijms21207579 |