Related Experiment Video

Updated: Jul 19, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1

Senthil K Radhakrishnan1, Uppoor G Bhat, Douglas E Hughes

  • 1Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

Cancer Research
|October 5, 2006
PubMed

Insights

Siomycin A, an antibiotic, inhibits the oncogenic transcription factor forkhead box M1 (FoxM1) in cancer cells. This inhibition reduces cancer cell growth and induces apoptosis, suggesting Siomycin A as a potential anticancer therapeutic starting point.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The transcription factor forkhead box M1 (FoxM1) is overexpressed in various carcinomas.
  • FoxM1 is a validated therapeutic target for cancer treatment due to its oncogenic role.
  • FoxM1 expression is silenced in terminally differentiated cells, distinguishing it from normal cells.

Purpose of the Study:

  • To identify inhibitors of the oncogenic transcription factor FoxM1.
  • To evaluate the potential of identified inhibitors as anticancer therapeutics.

Main Methods:

  • High-throughput, cell-based screening assay to identify FoxM1 inhibitors.
  • Assessed Siomycin A's effect on FoxM1 transcriptional activity, protein, and mRNA levels.
  • Investigated Siomycin A's impact on downstream FoxM1 target genes (Cdc25B, Survivin, CENPB), anchorage-independent growth, and apoptosis in cancer cells.

Main Results:

  • Siomycin A was identified as a potent inhibitor of FoxM1.
  • Siomycin A down-regulated FoxM1 expression and activity, repressing its target genes.
  • Siomycin A inhibited anchorage-independent cell growth and selectively induced apoptosis in cancer cells, sparing normal cells.

Conclusions:

  • Siomycin A effectively inhibits FoxM1, a key oncogenic transcription factor.
  • Siomycin A demonstrates anticancer properties, including reduced proliferation and induction of apoptosis.
  • Siomycin A serves as a promising lead compound for developing novel FoxM1-targeted anticancer therapies.

More Related Videos

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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...