Related Experiment Video

Updated: May 5, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

7.6K

Peroxisome proliferator-activated receptor γ ligand troglitazone and TRAIL synergistically induce apoptosis

Makoto Koyama1, Yoshihiro Sowa1, Mano Horinaka1

  • 1Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Oncology Reports
|November 27, 2013
PubMed

Insights

Troglitazone and TRAIL synergistically induce colon cancer cell death by increasing the DR5 receptor. This combination therapy shows promise for treating malignant tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via death receptor 5 (DR5).
  • Peroxisome proliferator-activated receptor γ (PPARγ) ligands, like troglitazone (TGZ), are investigated for anti-cancer properties.

Purpose of the Study:

  • To investigate the synergistic effect of troglitazone (TGZ) and TRAIL on apoptosis in human colon cancer cells.
  • To elucidate the mechanism of TGZ and TRAIL-induced apoptosis, focusing on DR5 expression.

Main Methods:

  • Human colon cancer DLD-1 cells were co-treated with TGZ and TRAIL.
  • DR5 expression levels and promoter activity were analyzed.
  • The role of CCAAT/enhancer-binding protein homologous protein (CHOP) in DR5 regulation was examined.

Main Results:

  • Co-treatment with TGZ and TRAIL synergistically enhanced apoptosis in DLD-1 cells.
  • TGZ upregulated DR5 expression at the transcriptional level.
  • TGZ-induced DR5 upregulation was mediated through the CHOP binding site on the DR5 promoter.

Conclusions:

  • Combined TGZ and TRAIL treatment effectively induces apoptosis in colon cancer cells.
  • DR5 upregulation, driven by TGZ via CHOP, is a key mechanism in this synergistic effect.
  • This combination therapy presents a potential new strategy for treating malignant tumors.

More Related Videos

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

38.4K
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.1K

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
998
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
1.3K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
1.1K
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...
5.2K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K