Article ; Online: Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.
2016 Volume 7, Issue 8, Page(s) 9462–9476
Abstract: ... Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate ... roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer ... anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3 ...
| Abstract | The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate the therapeutic potential of physalin A, a bioactive withanolide derived from Physalis alkekengi var. francheti used in traditional Chinese medicine, was evaluated in human NSCLC cells. Its and determined whether it effect oninhibited both constitutive and induced STAT3 activity, through repressing the phosphorylation levels of JAK2 and JAK3, resulting in anti-proliferation and pro-apoptotic effects on NSCLC cells was also determined, and. theThe antitumor effects of physalin A were also validated usingin an in vivo mouse xenograft models of NSCLC cells. Physalin A had anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore, physalin A abrogated the nuclear translocation and transcriptional activity of STAT3, thereby decreasing the expression levels of STAT3, its target genes, such as Bcl-2 and XIAP. Knockdown of STAT3 expression by small interfering RNA (siRNA) significantly enhanced the pro-apoptotic effects of physalin A in NSCLC cells. Moreover, physalin A significantly suppressed tumor xenograft growth. Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate the development of a therapeutic strategy for treating NSCLC. |
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| MeSH term(s) | A549 Cells ; Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Janus Kinase 2/antagonists & inhibitors ; Janus Kinase 2/metabolism ; Janus Kinase 3/antagonists & inhibitors ; Janus Kinase 3/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C ; Phosphorylation/drug effects ; Plant Preparations/pharmacology ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; RNA Interference ; RNA, Small Interfering/genetics ; STAT3 Transcription Factor/antagonists & inhibitors ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Transcription, Genetic/drug effects ; Withanolides/pharmacology ; X-Linked Inhibitor of Apoptosis Protein/biosynthesis ; Xenograft Model Antitumor Assays |
| Chemical Substances | Antineoplastic Agents ; Plant Preparations ; Proto-Oncogene Proteins c-bcl-2 ; RNA, Small Interfering ; STAT3 Transcription Factor ; STAT3 protein, human ; Withanolides ; X-Linked Inhibitor of Apoptosis Protein ; XIAP protein, human ; physalin A ; JAK2 protein, human (EC 2.7.10.2) ; JAK3 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2) |
| Language | English |
| Publishing date | 2016-02-23 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2560162-3 |
| ISSN | 1949-2553 ; 1949-2553 |
| ISSN (online) | 1949-2553 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.7051 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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