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Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.
- Source :
-
Oncotarget [Oncotarget] 2016 Feb 23; Vol. 7 (8), pp. 9462-76. - Publication Year :
- 2016
-
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.
- Subjects :
- A549 Cells
Animals
Antineoplastic Agents pharmacology
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Cell Proliferation drug effects
Gene Expression Regulation, Neoplastic drug effects
Humans
Janus Kinase 2 metabolism
Janus Kinase 3 metabolism
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 genetics
STAT3 Transcription Factor metabolism
Signal Transduction drug effects
Transcription, Genetic drug effects
X-Linked Inhibitor of Apoptosis Protein biosynthesis
Xenograft Model Antitumor Assays
Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung drug therapy
Janus Kinase 2 antagonists & inhibitors
Janus Kinase 3 antagonists & inhibitors
Lung Neoplasms drug therapy
STAT3 Transcription Factor antagonists & inhibitors
Withanolides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26843613
- Full Text :
- https://doi.org/10.18632/oncotarget.7051