Related Experiment Video

Updated: Aug 17, 2026

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth

Keiko Fukumoto1, Yoshihisa Yano, Nantiga Virgona

  • 1Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.

FEBS Letters
|June 28, 2005
PubMed

Insights

Prostaglandin I2 (PGI2) signaling inhibits lung cancer cell growth. Activating peroxisome proliferator-activated receptor delta (PPARdelta) is key to this PGI2 effect, especially when PG synthesis is suppressed.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Prostaglandin I2 (PGI2) signaling is hypothesized to inhibit lung cancer cell growth.
  • The precise molecular mechanisms underlying PGI2's growth-inhibitory effects remain unclear.
  • PGI2 signals via the G protein-coupled receptor IP and the nuclear receptor PPARdelta.

Purpose of the Study:

  • To elucidate the role of PPARdelta in PGI2-mediated negative growth control of lung cancer cells.
  • To investigate the interplay between PGI2 signaling, PPARdelta, and cyclooxygenase activity in lung cancer.

Main Methods:

  • Utilized carbarprostacyclin (a PGI2 agonist for IP and PPARdelta) and L-165041 (a PPARdelta agonist) on A549 lung cancer cells.
  • Assessed the impact of PPARdelta activation on cell growth.
  • Investigated the effect of cyclooxygenase inhibition in conjunction with PPARdelta activation.

Main Results:

  • PPARdelta was identified as a critical mediator of PGI2's negative growth control in A549 lung cancer cells.
  • Activation of PPARdelta significantly inhibited lung cancer cell proliferation.
  • Inhibition of cyclooxygenase enhanced the growth-suppressive effects mediated by PPARdelta.

Conclusions:

  • PPARdelta activation plays a crucial role in PGI2-dependent inhibition of lung cancer cell growth.
  • Suppression of prostaglandin synthesis enhances the anti-proliferative effects of PPARdelta.
  • Targeting PPARdelta activation, particularly under conditions of reduced prostaglandin production, may represent a therapeutic strategy for lung cancer.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal 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...
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...
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...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Targeted Cancer Therapies02:57

Targeted 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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...