Related Experiment Video

Updated: Aug 14, 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

Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid

I Avis1, S H Hong, A Martinez

  • 1Intervention Section, Department of Cell and Cancer Biology, Division of Clinical Sciences, National Cancer Institute, NIH Clinical Center, 9000 Rockville Pike, Bethesda, MD 20892-1906, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 21, 2001
PubMed

Insights

Inhibiting the 5-lipoxygenase (5-LO) pathway halts breast cancer cell growth and promotes apoptosis. This disruption impacts key proteins and activates specific receptors, offering a new therapeutic target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Arachidonic acid metabolites are crucial for epithelial cell growth signaling.
  • Previous studies identified arachidonic acid enzymes in human breast cancer cell lines.

Purpose of the Study:

  • To investigate the role of the 5-lipoxygenase (5-LO) pathway in regulating breast cancer cell growth.
  • To determine the effects of 5-LO pathway modulation on cancer cell proliferation and apoptosis.

Main Methods:

  • Human breast cancer cell lines were treated with growth factors (IGF-1, transferrin) to modulate 5-LO metabolite levels.
  • Radioimmunoassay and HPLC were used to quantify 5-HETE levels.
  • Cells were treated with 5-LO inhibitors, PPAR agonists, and cyclooxygenase inhibitors.

Main Results:

  • Insulin-like growth factor-1 and transferrin increased 5-lipoxygenase metabolite 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic acid (5-HETE) levels.
  • 5-HETE addition stimulated breast cancer cell growth; 5-LO inhibitors reduced 5-HETE, inhibited growth, and increased apoptosis.
  • 5-LO inhibition led to G1 arrest, altered bcl-2 and bax expression, and upregulated PPARa and PPARg.

Conclusions:

  • Disrupting the 5-LO signaling pathway induces growth arrest and apoptosis in breast cancer cells.
  • This process involves reduced 5-LO product stimulation and induced PPARg expression.
  • Potential activation of PPARg by shunted endoperoxides may contribute to therapeutic effects.

More Related Videos

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Related Concept Videos

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...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Lipid-derived Compounds in the Human Body01:31

Lipid-derived Compounds in the Human Body

Fats and lipids are crucial components in the human body. Some lipid-derived compounds, such as fat-soluble vitamins, eicosanoids, lipoproteins, and glycolipids, also play unique roles to support various  biological processes .
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin, delayed...