Related Experiment Video
Updated: Jun 4, 2026
07:02
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins
Sudhakar Chintharlapalli1, Sabitha Papineni, Syng-Ook Lee
1Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, USA.
Molecular Carcinogenesis
|January 27, 2011
Summary
New compounds derived from licorice, CDODA-Me and CF(3)DODA-Me, inhibit thyroid cancer growth by reducing specificity protein (Sp) transcription factors and PTTG-1. These findings suggest potential new treatments for thyroid cancer.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Thyroid cancer cells often overexpress specificity protein (Sp) transcription factors (Sp1, Sp3, Sp4).
- Pituitary tumor-transforming gene-1 (PTTG-1) is a pro-oncogenic factor overexpressed in endocrine neoplasias.
Purpose of the Study:
- To investigate the effects of novel synthetic compounds, CDODA-Me and CF(3)DODA-Me, derived from glycyrrhetinic acid, on thyroid cancer cell growth.
- To elucidate the molecular mechanisms underlying the anti-cancer effects of these compounds, focusing on Sp transcription factors and PTTG-1.
Main Methods:
- Synthesized CDODA-Me and CF(3)DODA-Me from glycyrrhetinic acid.
- Treated highly invasive thyroid cancer cell lines (ARO, DRO, K-18, HTh-74) with the compounds.
- Assessed changes in expression of Sp transcription factors, Sp-dependent genes (survivin, VEGF), PTTG-1, and PTTG-1-dependent genes (c-Myc, FGF-2).
- Utilized RNA interference to confirm the role of Sp proteins in PTTG-1 regulation.
Main Results:
- CDODA-Me and CF(3)DODA-Me significantly inhibited the growth of all tested thyroid cancer cell lines.
- Treatment led to decreased expression of Sp1, Sp3, and Sp4, as well as Sp-dependent genes survivin and VEGF.
- Both compounds reduced PTTG-1 protein and mRNA levels, along with PTTG-1-dependent genes c-Myc and FGF-2.
- RNA interference confirmed that PTTG-1 expression is dependent on Sp proteins in thyroid cancer cells.
Conclusions:
- CDODA-Me and CF(3)DODA-Me effectively inhibit thyroid cancer cell proliferation by downregulating Sp transcription factors and consequently PTTG-1.
- These compounds represent a promising therapeutic strategy for thyroid cancer and other endocrine neoplasias driven by PTTG-1.
Related Concept Videos
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
02:34Inhibition 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...
02:34Inhibition 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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...