Related Experiment Video

Updated: Jul 17, 2026

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

Cimetidine inhibits epidermal growth factor-induced cell signaling

Tatsuya Fujikawa1, Hidenori Shiraha, Yutaka Nakanishi

  • 1Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. tfmty@yahoo.co.jp

Journal of Gastroenterology and Hepatology
|February 14, 2007
PubMed
Abstract

Insights

Cimetidine inhibits liver cancer cell growth and migration by reducing intracellular cyclic AMP (cAMP) levels. This finding suggests cimetidine

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cimetidine, a histamine-2 (H2) receptor antagonist, exhibits anticancer properties against various cancers.
  • Previous studies indicated cimetidine's efficacy in colorectal cancer, melanoma, and renal cell carcinoma.
  • This research investigates cimetidine's effects on hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To investigate the inhibitory effects of cimetidine on epidermal growth factor (EGF)-induced cell proliferation and migration in hepatocellular carcinoma (HCC) cell lines.
  • To elucidate the molecular mechanisms underlying cimetidine's action in HCC.
  • To evaluate cimetidine as a potential chemopreventive agent for HCC.

Main Methods:

  • Utilized multiple HCC cell lines (Hep3B, HLF, SK-Hep-1, JHH-2, PLC/PRF/5, HLE).
  • Assessed cell proliferation via [3H]-thymidine incorporation and cell migration using in vitro assays.
  • Analyzed EGF receptor (EGFR) autophosphorylation, downstream signaling pathways, and intracellular cyclic AMP (cAMP) levels.

Main Results:

  • Cimetidine inhibited EGF-induced proliferation and migration in specific HCC cell lines (Hep3B, HLF, SK-Hep-1, JHH-2).
  • Cimetidine disrupted EGF-induced EGFR autophosphorylation and downstream signaling (MAPK, PLC-gamma).
  • Cimetidine decreased intracellular cAMP levels, which was identified as the mechanism inhibiting EGFR autophosphorylation. Restoration of cAMP levels reversed these effects.

Conclusions:

  • Cimetidine inhibits EGF-induced proliferation and migration in HCC cell lines by reducing intracellular cAMP levels.
  • The findings suggest cimetidine's potential as a chemopreventive agent for HCC.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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...