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.

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.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
12.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K