Related Experiment Video

Updated: Aug 16, 2026

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine

Masaaki Nomura1, Daisuke Ichimatsu, Shuzo Moritani

  • 1Department of Hospital Pharmacy, School of Medicine, Kanazawa University, Kanazawa, Japan.

Molecular Carcinogenesis
|July 27, 2005
PubMed

Insights

Caffeine inhibits tumor promoter-induced cell transformation by blocking key signaling pathways like Akt. This research offers new insights into caffeine's potential chemotherapeutic effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cell transformation is a critical step in cancer development.
  • Epidermal Growth Factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are known inducers of cell transformation.
  • The signaling pathways involved in cell transformation are complex and represent potential therapeutic targets.

Purpose of the Study:

  • To investigate the effect of caffeine on EGF- and TPA-induced cell transformation.
  • To elucidate the molecular mechanisms underlying caffeine's potential chemopreventive properties.

Main Methods:

  • Utilized the JB6 mouse epidermal cell line for transformation assays.
  • Administered caffeine and an adenosine A1 receptor antagonist (8-phenyltheophylline) to assess inhibition.
  • Analyzed the activation of key signaling molecules, including Activator Protein 1 (AP-1), Akt, and p70 S6 Kinase (p70S6K), using Western blotting or similar techniques.
  • Investigated the effect on Phosphatidylinositol 3-Kinase (PI3K) activation.

Main Results:

  • Caffeine significantly inhibited EGF- and TPA-induced cell transformation.
  • The adenosine A1 receptor antagonist 8-phenyltheophylline also blocked tumor promoter-induced transformation.
  • Caffeine showed a slight attenuation of EGF-induced Activator Protein 1 (AP-1) activation at high concentrations.
  • Caffeine suppressed EGF-induced phosphorylation and activation of Akt and its downstream target, p70 S6 Kinase (p70S6K).
  • Crucially, caffeine did not inhibit Phosphatidylinositol 3-Kinase (PI3K) activation, and its effect on Akt was independent of adenosine receptor antagonism.

Conclusions:

  • Caffeine exhibits chemopreventive effects against induced cell transformation.
  • The inhibition of Akt signaling, independent of adenosine receptor antagonism, is a key mechanism for caffeine's effect.
  • These findings provide novel insights into the chemotherapeutic potential of caffeine, highlighting its role in modulating critical cancer-related signaling pathways.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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 rapamycin-insensitive companion...
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...