Related Experiment Video

Updated: Aug 4, 2025

Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
07:15

Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)

Published on: July 3, 2025

170

Intracellular cGMP increase is not involved in thyroid cancer cell death

Sara D' Alessandro1,2, Elia Paradiso1, Clara Lazzaretti1

  • 1Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Plos One
|March 30, 2023
PubMed
Abstract

Insights

Type 5 phosphodiesterase inhibitors (PDE5i) did not affect thyroid cancer cell growth or viability in vitro. Increased cyclic-guanosine monophosphate (cGMP) levels from PDE5i treatment did not lead to cell death, suggesting no impact on thyroid cancer risk.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Type 5 phosphodiesterase inhibitors (PDE5i) increase intracellular cyclic-guanosine monophosphate (cGMP).
  • cGMP's role in endocrine tumor cell growth suggests PDE5i may influence cancer risk.
  • The impact of PDE5i on thyroid cancer remains unclear.

Purpose of the Study:

  • To investigate the effect of PDE5 inhibitors on thyroid cancer cell growth in vitro.
  • To determine if PDE5 inhibitors modulate cell viability and proliferation markers in thyroid cancer cells.

Main Methods:

  • Utilized malignant (K1) and benign (Nthy-ori 3-1) thyroid cell lines.
  • Treated cells with vardenafil (a PDE5 inhibitor) or 8-br-cGMP (a cGMP analog).
  • Assessed cGMP levels, caspase 3 activation, ERK1/2 phosphorylation, nuclear fragmentation, and cell viability.

Main Results:

  • Vardenafil and 8-br-cGMP increased intracellular cGMP levels in a dose-dependent manner.
  • No significant differences in caspase 3 activation, nuclear fragmentation, or ERK1/2 phosphorylation were observed.
  • PDE5i treatment did not impact the viability of malignant or benign thyroid cell lines.

Conclusions:

  • Elevated cGMP levels do not influence cell viability or death in thyroid cancer cell lines.
  • PDE5 inhibitors do not appear to affect the growth of thyroid cancer cells in vitro.
  • Further research is recommended to fully elucidate the impact of PDE5i on thyroid cancer.

More Related Videos

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.4K
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.0K

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.1K
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
7.1K
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,...
6.5K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
4.7K