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STAT3-mediated Apoptotic-enhancing Function of Sclareol Against Breast Cancer Cells and Cell Sensitization to
Havva Afshari1, Mitra Nourbakhsh2, Niloufar Salehi1
1Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran .
Abstract:
Sclareol is an organic compound with potential anti-tumor effects against various cancer types. However, its precise molecular mechanism in the suppression of tumor growth has not been fully elucidated. In the present study, the anti-proliferative and apoptosis-inducing effects of sclareol with cyclophosphamide were investigated in breast cancer cells and the involvement of the JAK/STAT pathway was evaluated. For this purpose, MCF-7 breast cancer cells were cultured and treated with various concentrations of sclareol to determine its IC50. Cell viability was measured by MTT assay and apoptosis was assessed by flow cytometric analysis of annexin V binding. Gene and protein expression were examined by real-time PCR and Western blotting, respectively. The activity of caspase enzymes was also measured. The results showed that sclareol significantly reduced cell viability and triggered cell death and its co-administration with cyclophosphamide enhanced its anti-cancer properties. Additionally, sclareol up-regulated the expression of p53 and BAX and reduced the expression of Bcl-2. Docking studies indicated an interaction between sclareol and STAT3 which was proved by attenuation of STAT3 phosphorylation after treatment of the cells with sclareol. Sclareol was also capable of suppressing the function of IL-6 in modulating the expression of apoptosis-associated genes. Altogether these data suggest the potential of sclareol as an anti-cancer agent and demonstrate that a combination of sclareol with cyclophosphamide might serve as an effective chemotherapeutic approach resulting in improvements in the treatment of breast cancer.
Insights
Sclareol, an organic compound, effectively reduces breast cancer cell viability and induces apoptosis. Combining sclareol with cyclophosphamide enhances anti-cancer properties by targeting the JAK/STAT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Sclareol exhibits potential anti-tumor effects, but its molecular mechanisms in cancer suppression require further elucidation.
- Understanding sclareol's action is crucial for developing novel breast cancer therapies.
Purpose of the Study:
- To investigate the anti-proliferative and apoptosis-inducing effects of sclareol, alone and with cyclophosphamide, in breast cancer cells.
- To evaluate the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in sclareol's anti-cancer activity.
Main Methods:
- MCF-7 breast cancer cells were treated with sclareol to determine IC50, cell viability (MTT assay), and apoptosis (Annexin V flow cytometry).
- Gene and protein expression (p53, BAX, Bcl-2, STAT3) were analyzed via real-time PCR and Western blotting.
- Caspase activity, STAT3 phosphorylation, and IL-6 signaling were assessed.
Main Results:
- Sclareol significantly decreased cell viability and induced apoptosis in breast cancer cells.
- Co-administration of sclareol and cyclophosphamide potentiated anti-cancer effects.
- Sclareol modulated apoptosis-related gene/protein expression (upregulated p53, BAX; downregulated Bcl-2) and inhibited STAT3 phosphorylation.
- Sclareol suppressed IL-6's role in regulating apoptosis-associated gene expression.
Conclusions:
- Sclareol demonstrates significant anti-cancer properties against breast cancer cells.
- The combination of sclareol and cyclophosphamide presents a promising chemotherapeutic strategy.
- Sclareol's mechanism involves the JAK/STAT pathway, offering potential for improved breast cancer treatment.
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