Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death
| العنوان: | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
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| المؤلفون: | Roberta Santarelli, Mara Cirone, Marisa Granato, Alberto Faggioni, Maria Saveria Gilardini Montani, Gabriella D'Orazi |
| المصدر: | Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-9 (2017) Journal of Experimental & Clinical Cancer Research : CR |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, p53, 0301 basic medicine, Cancer Research, Programmed cell death, Cell Survival, Apoptosis, KSHV, lcsh:RC254-282, STAT3, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Lymphoma, Primary Effusion, Autophagy, medicine, Humans, Gene silencing, Phosphorylation, Apigenin, Cell Proliferation, PEL, vFLIP, biology, Research, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Antineoplastic Agents, Phytogenic, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Primary effusion lymphoma, Tumor Suppressor Protein p53, Reactive Oxygen Species, Intracellular |
| الوصف: | Background Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very aggressive behavior, displaying constitutive activation of STAT3 as well as of other oncogenic pathways and harboring wtp53. Methods Cell death was assessed by trypan blue exclusion assay, FACS analysis as well as by biochemical studies. The latter were also utilized to detect the occurrence of autophagy and the molecular mechanisms leading to the activation of both processes by apigenin. FACS analysis was used to measure the intracellular ROS utilizing DCFDA. Results We show that apigenin induced PEL cell death and autophagy along with reduction of intracellular ROS. Mechanistically, apigenin activated p53 that induced catalase, a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival pathway in PEL, as assessed by p53 silencing. On the other hand, STAT3 inhibition by apigenin resulted in p53 activation, since STAT3 negatively influences p53 activity, highlighting a regulatory loop between these two pathways that modulates PEL cell death/survival. Conclusion The findings of this study demonstrate that apigenin may modulate pro-apoptotic and pro-survival pathways representing a valid therapeutic strategy against PEL. |
| تدمد: | 1756-9966 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d40c71f4c4c6d4eb96bbd597eba49f8Test https://doi.org/10.1186/s13046-017-0632-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9d40c71f4c4c6d4eb96bbd597eba49f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17569966 |
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