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Inhibition of tetrandrine on epidermal growth factor-induced cell transformation and its signal transduction
Masaaki Nomura1, Rina Yamazaki, Makiko Takaya
1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, and Hokuriku University, Kanazawa, Japan.
Background:
The mouse epidermal JB6 cell system is a model for studying tumor promotion. We used the JB6 Cl 41 cell line to examine the mechanism of the anti-tumor-promoting effect of tetrandrine, an alkaloid isolated from Stephania tetrandra S Moore.
Materials And Methods:
The anti-tumor-promoting effect of tetrandrine was evaluated by assay of inhibition of epidermal growth factor (EGF)-induced transformation of JB6 Cl 41 cells in soft agar. The activity of activator protein-1 (AP-1), a transcription factor, was analyzed using the AP-1-dependent reporter assay. Phosphorylation of extracellular-signal regulated kinases (ERKs) and Akt, a pivotal effector of phosphatidylinositol 3-kinase (P13K), was detected by Western blotting.
Results:
Tetrandrine significantly blocked EGF-induced cell transformation, attenuated EGF-induced AP-1 activation, and inhibited phosphorylation of ERKs, which regulates AP-1 activation. It also tended to suppress EGF-induced Akt phosphorylation.
Conclusion:
Our results indicate that tetrandrine inhibits EGF-induced transformation of JB6 cells by blocking the activation of ERKs, AP-1 and Akt.
Insights
Tetrandrine, a natural alkaloid, inhibits skin tumor promotion by blocking key signaling pathways. It suppresses epidermal growth factor-induced cell transformation and the activation of transcription factor AP-1 and ERKs.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- The mouse JB6 epidermal cell system is utilized to investigate tumor promotion mechanisms.
- Tetrandrine, an alkaloid from Stephania tetrandra S Moore, is examined for its anti-tumor-promoting properties.
Purpose of the Study:
- To elucidate the mechanism by which tetrandrine exerts its anti-tumor-promoting effect.
- To investigate tetrandrine's impact on epidermal growth factor (EGF)-induced transformation in JB6 Cl 41 cells.
Main Methods:
- Assessed tetrandrine's inhibition of EGF-induced JB6 Cl 41 cell transformation in soft agar.
- Analyzed activator protein-1 (AP-1) activity using an AP-1-dependent reporter assay.
- Detected phosphorylation of extracellular-signal regulated kinases (ERKs) and Akt via Western blotting.
Main Results:
- Tetrandrine significantly inhibited EGF-induced cell transformation and AP-1 activation.
- Tetrandrine suppressed the phosphorylation of ERKs, a key regulator of AP-1.
- A trend towards suppressed EGF-induced Akt phosphorylation was observed.
Conclusions:
- Tetrandrine inhibits EGF-induced transformation in JB6 cells.
- The anti-tumor-promoting effect is mediated by blocking the activation of ERKs, AP-1, and potentially Akt.
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