Paclitaxel induces apoptosis of esophageal squamous cell carcinoma cells by downregulating STAT3 phosphorylation at
Xiaolong Zhang1, Xiaoyi Wu2, Fangling Zhang3
1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Abstract:
Paclitaxel induces apoptosis in a variety of cancer cells. However, the mechanism of paclitaxel inducing apoptosis in human esophageal squamous cell carcinoma (ESCC) remains to be defined. In this study, we found that paclitaxel-induced apoptosis by increasing the relevant apoptosis protein expression and the release of cytochrome c via downregulation of signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (Ser727). In addition, paclitaxel treatment of ESCC cells EC-1 and Eca-109 led to marked mitochondrial membrane potential depolarization and significantly increasing of reactive oxygen species. Moreover, paclitaxel treatment resulted in the inhibition of mitochondrial respiration. In conclusion, our findings reveal that paclitaxel induced apoptosis in both EC-1 and Eca-109 cells through the reduction of STAT3 and phospho‑STAT3 (Ser727) level, and suggest that paclitaxel may be of therapeutic potential in the treatment of ESCC through the induction of mitochondrial apoptosis in ESCC cells.
Insights
Paclitaxel triggers cancer cell death by impacting mitochondrial function and reducing STAT3 signaling. This study clarifies paclitaxel
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Paclitaxel is a known inducer of apoptosis in various cancer types.
- The precise mechanisms by which paclitaxel induces apoptosis in human esophageal squamous cell carcinoma (ESCC) are not fully elucidated.
Purpose of the Study:
- To investigate the molecular mechanisms underlying paclitaxel-induced apoptosis in human ESCC cells.
- To explore the role of Signal Transducer and Activator of Transcription 3 (STAT3) signaling in paclitaxel's apoptotic effects on ESCC.
Main Methods:
- Treatment of ESCC cell lines (EC-1 and Eca-109) with paclitaxel.
- Assessment of apoptosis-related protein expression and cytochrome c release.
- Measurement of mitochondrial membrane potential and reactive oxygen species (ROS) production.
- Analysis of mitochondrial respiration and STAT3/phospho-STAT3 levels.
Main Results:
- Paclitaxel treatment upregulated apoptosis-related proteins and increased cytochrome c release.
- Downregulation of Signal Transducer and Activator of Transcription 3 (STAT3) and phospho-STAT3 (Ser727) was observed.
- Paclitaxel induced mitochondrial membrane potential depolarization and increased ROS generation.
- Inhibition of mitochondrial respiration was noted following paclitaxel treatment.
Conclusions:
- Paclitaxel induces apoptosis in ESCC cells (EC-1 and Eca-109) by downregulating STAT3 and phospho-STAT3 (Ser727).
- The findings highlight paclitaxel's role in inducing mitochondrial apoptosis in ESCC.
- Paclitaxel demonstrates therapeutic potential for ESCC treatment via mitochondrial apoptotic pathways.
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