Related Experiment Video

Updated: Jun 22, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

PPARgamma activation induces autophagy in breast cancer cells

Jie Zhou1, Wei Zhang, Bing Liang

  • 1Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.

The International Journal of Biochemistry & Cell Biology
|July 1, 2009
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARγ) ligands induce autophagy, not apoptosis, in breast cancer cells. This activation involves HIF1α and BNIP3, offering new insights into PPARγ

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) ligands are known to induce apoptosis in cancer cells.
  • Previous studies suggested receptor-independent functions for these ligands.
  • The precise role of PPARγ activation in cancer cell death pathways requires further investigation.

Purpose of the Study:

  • To investigate the specific role of PPARγ activation in breast cancer cell death.
  • To determine if PPARγ ligands induce apoptosis or another cell death pathway in MDA-MB-231 cells.
  • To elucidate the molecular mechanism underlying PPARγ-mediated effects on breast cancer cells.

Main Methods:

  • Treatment of MDA-MB-231 breast cancer cells with synthetic PPARγ ligands (troglitazone, rosiglitazone).
  • Assessment of apoptosis using standard assays.
  • Acridine orange staining to detect acidic vesicular formation (autophagy).
  • Analysis of autophagosome formation via LC3 redistribution and electron microscopy.
  • Gene expression analysis (genome-wide array) in primary mammary epithelial cells transduced with a constitutively active PPARγ mutant.
  • Validation of target gene (HIF1α, BNIP3) expression at protein and mRNA levels.
  • Knockdown of HIF1α using shRNA to assess its role in autophagy.

Main Results:

  • PPARγ ligands did not induce apoptosis in MDA-MB-231 cells at sub-saturation doses.
  • Evidence of autophagic activity, including acidic vesicular and autophagosome formation, was observed.
  • PPARγ activation upregulated 42 genes, including HIF1α and BNIP3.
  • PPARγ activation increased HIF1α and BNIP3 protein and mRNA levels.
  • HIF1α knockdown abrogated PPARγ-induced autophagosome formation.

Conclusions:

  • PPARγ activation specifically induces autophagy in breast cancer cells, rather than apoptosis.
  • The mechanism involves the upregulation of HIF1α and BNIP3.
  • These findings highlight distinct roles for PPARγ in tumorigenesis, focusing on autophagy induction.

More Related Videos

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase09:51

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence08:07

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence

Published on: April 28, 2023

Related Concept Videos

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...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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...