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Icariside II inhibits tumorigenesis via inhibiting AKT/Cyclin E/ CDK 2 pathway and activating mitochondria-dependent
Ya-Sai Sun1, Kiran Thakur1, Fei Hu1
1School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, PR China.
Abstract:
Cervical cancer contributes largely in women cancer-related mortality. Herein, Icariside II, a flavonoid extracted from edible and pharmaceutical plant Epimedium brevicornum Maxim, exhibited significant anticancer activity on cervical cancer. At first, it was observed that Icariside II inhibited Hela cell proliferation at IC50 (9.2 μM) and the growth of Hela-originated xenografts in BALB/c nude mice. Next, we studied the underlying mechanisms of Icariside II from the aspects of cell growth and cell death. As for cell growth, Icariside II arrested cell cycle at G0/G1 phase through AKT/Cyclin E/CDK 2 from transcriptional and translational levels. As for cell death, Flow Cytometry and Immunofluorescence showed that Icariside II promoted cell death in a dose-dependet manner. And, Icariside II turned to activate the mitochondria-dependent pathway Caspase 9/Caspase 3 much more significantly than death receptor pathway Caspase 8/Caspase 3. Taken together, Icariside II presented anticancer effect on cervical cancer both in vitro and in vivo. Our study provides the evidence that Icariside II can be used as a suitable novel agent in cervical cancer treatment.
Insights
Icariside II, a compound from Epimedium brevicornum, shows potent anticancer effects against cervical cancer. It inhibits cancer cell growth and triggers cell death, suggesting its potential as a novel therapeutic agent.
Area of Science:
- Pharmacology
- Oncology
- Natural Products
Background:
- Cervical cancer is a leading cause of cancer-related mortality in women worldwide.
- There is an ongoing need for novel therapeutic agents to improve cervical cancer treatment outcomes.
Purpose of the Study:
- To investigate the anticancer activity of Icariside II, a flavonoid from Epimedium brevicornum, against cervical cancer.
- To elucidate the underlying mechanisms of Icariside II's action on cervical cancer cells.
Main Methods:
- In vitro studies using Hela cells to assess proliferation inhibition (IC50) and cell cycle arrest.
- In vivo studies using Hela-originated xenografts in BALB/c nude mice to evaluate tumor growth inhibition.
- Flow cytometry and immunofluorescence assays to analyze Icariside II-induced cell death pathways.
Main Results:
- Icariside II significantly inhibited Hela cell proliferation with an IC50 of 9.2 μM and suppressed xenograft tumor growth.
- Icariside II induced G0/G1 cell cycle arrest by modulating the AKT/Cyclin E/CDK 2 pathway.
- Icariside II promoted apoptosis via the mitochondria-dependent pathway (Caspase 9/Caspase 3) more effectively than the death receptor pathway (Caspase 8/Caspase 3).
Conclusions:
- Icariside II demonstrates significant in vitro and in vivo anticancer effects against cervical cancer.
- The findings support Icariside II as a promising novel therapeutic agent for cervical cancer treatment.
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