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Berberine Increases Doxorubicin Sensitivity by Suppressing STAT3 in Lung Cancer
Ting Zhu1, Lin-Lin Li1, Guang-Fa Xiao2
1* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Abstract:
Berberine (BBR), an alkaloid component isolated from Chinese medicinal herb Huang Lian, has aroused broad interests for its antitumor effect in recent years. The signal transducer and activator of transcription 3 (STAT3), plays critical roles in malignant transformation and progression and was found to be constitutively activated in a variety of human cancers. In this study, we show that BBR inhibited cell proliferation, induced apoptosis, and suppressed tumor spheroid formation of lung cancer cell lines. These effects were correlated with BBR-mediated suppression of both phosphorylated and total levels of STAT3 protein. Furthermore, BBR promoted STAT3 degradation by enhancing ubiquitination. Importantly, we demonstrated that BBR was able to inhibit doxorubicin (DOX)-mediated STAT3 activation and sensitize lung cancer cells to the cytotoxic effect of DOX treatment. Given that BBR is widely used in clinic with low toxicity, our results are potentially important for the development of a novel combinatorial therapy with BBR and DOX in the treatment of lung cancer.
Insights
Berberine (BBR) inhibits lung cancer progression by suppressing STAT3 signaling. This natural compound also enhances the effectiveness of doxorubicin (DOX) chemotherapy, suggesting a potential new combination therapy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is crucial in cancer development and often constitutively activated in various human cancers.
- Berberine (BBR), an alkaloid from Huang Lian, exhibits promising antitumor properties.
- Constitutive STAT3 activation is implicated in lung cancer malignancy and progression.
Purpose of the Study:
- To investigate the antitumor effects of Berberine (BBR) on lung cancer cells.
- To elucidate the mechanism of BBR's action, focusing on STAT3 signaling.
- To evaluate the potential of BBR in combination with doxorubicin (DOX) for lung cancer treatment.
Main Methods:
- Assessed BBR's effects on lung cancer cell proliferation, apoptosis, and tumor spheroid formation.
- Analyzed BBR's impact on both phosphorylated and total STAT3 protein levels.
- Investigated BBR's influence on STAT3 ubiquitination and degradation.
- Examined BBR's ability to modulate doxorubicin (DOX)-induced STAT3 activation and cytotoxicity.
Main Results:
- BBR significantly inhibited lung cancer cell proliferation, induced apoptosis, and suppressed tumor spheroid formation.
- BBR treatment led to decreased levels of phosphorylated and total STAT3.
- BBR enhanced STAT3 degradation through increased ubiquitination.
- BBR suppressed doxorubicin (DOX)-mediated STAT3 activation and sensitized lung cancer cells to DOX treatment.
Conclusions:
- Berberine (BBR) demonstrates potent antitumor activity against lung cancer by inhibiting STAT3 signaling.
- BBR promotes STAT3 degradation, contributing to its antiproliferative and pro-apoptotic effects.
- BBR shows potential as a sensitizer for doxorubicin (DOX) chemotherapy, offering a novel therapeutic strategy for lung cancer.
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