Genistein, a dietary isoflavone, down-regulates the MDM2 oncogene at both transcriptional and posttranslational

Related Experiment Video

Updated: Aug 15, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Mao Li1, Zhuo Zhang, Donald L Hill

  • 1Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, 35294, USA.

Cancer Research
|September 17, 2005
PubMed

Insights

Genistein, a compound found in soy, reduces levels of the MDM2 oncogene through novel mechanisms. This action may explain genistein's anticancer effects in breast, colon, and prostate cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Genistein exhibits chemopreventive properties against various human cancers.
  • The precise mechanisms underlying genistein's anticancer activities remain incompletely elucidated.

Purpose of the Study:

  • To investigate novel mechanisms by which genistein exerts its anticancer effects.
  • To determine if genistein down-regulates the MDM2 oncogene.

Main Methods:

  • Genistein's effect on MDM2 protein and mRNA levels was assessed in various human cancer cell lines and primary cells.
  • Transcriptional regulation via the MDM2 P2 promoter and posttranslational regulation through ubiquitination and degradation were analyzed.
  • Genistein's impact on apoptosis, cell cycle arrest, proliferation, and tumor growth in xenografts was evaluated.

Main Results:

  • Genistein dose-dependently reduced MDM2 protein and mRNA levels.
  • Inhibition occurred at both transcriptional and posttranslational levels, involving NFAT site activity and MDM2 ubiquitination/degradation.
  • Genistein induced apoptosis, G2 arrest, and inhibited proliferation, effects that were independent of p53 status and abrogated by MDM2 overexpression.

Conclusions:

  • Genistein directly down-regulates the MDM2 oncogene via transcriptional and posttranslational mechanisms.
  • This novel mechanism contributes to genistein's anticancer activities, including apoptosis induction and proliferation inhibition.
  • These findings suggest potential chemopreventive and chemotherapeutic applications for genistein in cancers driven by MDM2.

More Related Videos

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.