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Published on: June 9, 2023
Ellagic Acid Enhances the Efficacy of PI3K Inhibitor GDC-0941 in Breast Cancer Cells
1Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China. pixu_liu@dlmedu.edu.cn.
Abstract:
The fact that the phosphatidylinositol 3 kinase (PI3K) signaling pathway is one of the most frequently deregulated signaling networks has triggered intensive efforts in the development of PI3K pathway inhibitors. However, recent clinical trial data have shown only limited activity of PI3K inhibitors at tolerated doses. Thus, there is an urgent need to identify rational combination therapy to improve the efficacy of PI3K-targeted cancer treatment. In this study, we investigated if dietary compound ellagic acid (EA) could improve the therapeutic efficacy of PI3K inhibitor GDC-0941 in breast cancer. Specifically, using a panel of breast cancer cell lines, we showed that combined use of EA and GDC-0941 significantly inhibited cell growth under attached and detached conditions, blocked migration and invasion in vitro as well as tumor initiation and metastasis in vivo. Furthermore, we found that EA promoted apoptosis and further reduced AKT/mTOR activation in GDC-0941- treated breast cancer cells. Together, our data suggest that EA may be a safe and effective agent to boost the efficacy of PI3K-directed breast cancer therapy and that such drug combination may merit further clinical investigation.
Insights
Dietary ellagic acid (EA) enhances the effectiveness of PI3K inhibitors like GDC-0941 in breast cancer treatment. This combination therapy inhibits cancer cell growth, migration, and metastasis, offering a promising strategy for improved patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The phosphatidylinositol 3 kinase (PI3K) signaling pathway is frequently deregulated in cancer.
- Current PI3K inhibitors show limited efficacy at tolerated doses, necessitating combination therapies.
- Developing strategies to enhance PI3K-targeted cancer treatment is crucial.
Purpose of the Study:
- To investigate the potential of dietary ellagic acid (EA) to improve the therapeutic efficacy of the PI3K inhibitor GDC-0941 in breast cancer.
- To evaluate the combined effects of EA and GDC-0941 on breast cancer cell growth, invasion, and metastasis.
Main Methods:
- Utilized a panel of breast cancer cell lines for in vitro studies.
- Assessed cell growth, migration, and invasion under combined EA and GDC-0941 treatment.
- Evaluated tumor initiation and metastasis in vivo models.
- Analyzed apoptosis and AKT/mTOR pathway activation.
Main Results:
- Combined EA and GDC-0941 significantly inhibited breast cancer cell growth (attached and detached conditions).
- The combination treatment blocked cancer cell migration and invasion in vitro.
- In vivo studies demonstrated reduced tumor initiation and metastasis with combined therapy.
- EA enhanced apoptosis and further suppressed AKT/mTOR activation in GDC-0941-treated cells.
Conclusions:
- Ellagic acid (EA) can serve as a safe and effective agent to potentiate PI3K-targeted breast cancer therapy.
- The combination of EA with PI3K inhibitors warrants further clinical investigation for breast cancer treatment.
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