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Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling
Kangdong Liu1,2,3,4, Chanmi Park1,5, Hanyong Chen2
1World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Abstract:
Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.
Insights
Eupafolin, a natural compound, inhibits prostate cancer growth by targeting the PI3-K/Akt pathway. This compound reduces cancer cell proliferation and tumor development, offering potential for new cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Loss of Phosphatase and tensin homolog (PTEN) activates the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, driving prostate cancer progression and invasiveness.
- The PTEN/PI3-K/Akt pathway, along with Ras/MAPK, promotes epithelial-mesenchymal transition (EMT) and metastasis from prostate stem/progenitor cells.
- The PTEN/PI3-K/Akt pathway is a key target for prostate cancer chemoprevention and chemotherapy.
Purpose of the Study:
- To investigate the antitumor effects of eupafolin, a natural compound from common sage, on prostate cancer.
- To elucidate the molecular mechanisms underlying eupafolin's action, specifically its effect on the PI3-K/Akt pathway.
Main Methods:
- Prostate cancer cell proliferation assays.
- Protein analysis to assess Akt phosphorylation and downstream kinase activity.
- Pull-down assays and in vitro kinase assays to determine eupafolin's interaction with PI3-K.
- In vivo tumor suppression studies in an athymic nude mouse model.
Main Results:
- Eupafolin significantly inhibited prostate cancer cell proliferation.
- Eupafolin treatment reduced the phosphorylation of Akt and its downstream kinases.
- Eupafolin directly binds to PI3-K and attenuates its kinase activity.
- Eupafolin demonstrated tumor suppressive effects in vivo.
Conclusions:
- Eupafolin exhibits potent antitumor effects against prostate cancer.
- Eupafolin's mechanism of action involves the direct inhibition of PI3-K activity.
- Eupafolin represents a promising natural compound for prostate cancer chemoprevention and chemotherapy targeting the PI3-K pathway.
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