Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling
Related Experiment Video
Updated: Oct 23, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Fanfan Zhu1, Chunyan Dai1, Yufei Fu1
1Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, PR China.
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.
Insights
Physalin A, a natural compound, effectively inhibits cancer cell growth and promotes cell death in non-small cell lung cancer (NSCLC) by targeting the STAT3 pathway. This compound shows significant anti-tumor effects in both cell cultures and animal models.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The Signal Transducers and Activators of Transcription 3 (STAT3) pathway is crucial in the development and progression of various cancers, including non-small cell lung cancer (NSCLC).
- Targeting the STAT3 pathway presents a promising therapeutic strategy for managing NSCLC.
Purpose of the Study:
- To investigate the anti-cancer potential of physalin A, a natural compound from Physalis alkekengi var. francheti, in human NSCLC cells.
- To determine if physalin A inhibits STAT3 signaling by modulating JAK2 and JAK3 activity.
- To evaluate the anti-proliferative and pro-apoptotic effects of physalin A in NSCLC.
Main Methods:
- Treatment of human NSCLC cells with physalin A.
- Assessment of STAT3 phosphorylation, JAK2/JAK3 activity, and expression of STAT3 target genes (Bcl-2, XIAP).
- Validation of anti-tumor effects using in vivo mouse xenograft models.
- STAT3 knockdown using small interfering RNA (siRNA).
Main Results:
- Physalin A demonstrated significant anti-proliferative and pro-apoptotic effects in NSCLC cells, particularly those with activated STAT3.
- Physalin A suppressed both constitutive and induced STAT3 activity by reducing JAK2 and JAK3 phosphorylation.
- The compound inhibited STAT3 nuclear translocation and transcriptional activity, leading to decreased expression of Bcl-2 and XIAP.
- STAT3 knockdown potentiated the pro-apoptotic effects of physalin A.
- Physalin A significantly inhibited tumor growth in NSCLC xenograft models.
Conclusions:
- Physalin A exhibits potent anti-tumor activities against NSCLC by inhibiting the JAK2/3-STAT3 signaling pathway.
- Physalin A represents a potential therapeutic agent for NSCLC treatment.
- Further development of physalin A as a therapeutic strategy for NSCLC is warranted.
