Related Experiment Video

Updated: Jan 6, 2026

Evaluating In Vitro DNA Damage Using Comet Assay
10:43

Evaluating In Vitro DNA Damage Using Comet Assay

Published on: October 11, 2017

39.3K

Histone demethylase KDM4C confers temozolomide resistance to glioblastoma cells by epigenetically regulating E2F6

Go Woon Kim1, Dong Hoon Lee1, Jung Yoo1

  • 1College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-Ro, Yeonsu-Gu, Incheon, 21983, Republic of Korea.

Archives of Pharmacal Research
|November 11, 2025
PubMed

Insights

Targeting KDM4C epigenetically upregulates E2F6, overcoming temozolomide (TMZ) resistance in glioblastoma (GBM). Inhibiting KDM4C with SD70 synergizes with TMZ, restoring sensitivity and offering a new GBM treatment strategy.

Area of Science:

  • Neuro-oncology
  • Epigenetics
  • Cancer Pharmacology

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
  • Temozolomide (TMZ) resistance is a major challenge, leading to treatment failure.
  • Identifying novel therapeutic targets is crucial for overcoming GBM chemoresistance.

Purpose of the Study:

  • To identify an epigenetic target to overcome temozolomide (TMZ) resistance in glioblastoma (GBM).
  • To investigate the role of KDM4C in TMZ resistance.
  • To evaluate KDM4C inhibition as a therapeutic strategy for GBM.

Main Methods:

  • Established TMZ-resistant GBM cell lines.
  • Conducted KDM inhibitor screening.
  • Utilized pharmacological inhibition (SD70) and genetic approaches.
  • Analyzed gene expression (E2F6, ABCG2, STAT3, Bax) and protein interactions.
  • Performed cell viability, proliferation, and stem-like property assays.

Main Results:

  • TMZ-resistant GBM cells showed increased E2F6, ABCG2, p-STAT3, and decreased Bax.
  • KDM4C was identified as a key therapeutic target.
  • KDM4C inhibition (SD70) reduced viability, proliferation, and stem-like properties of resistant cells.
  • Combination treatment with SD70 and TMZ demonstrated synergistic effects, restoring TMZ sensitivity.
  • KDM4C directly regulated E2F6 expression by binding to its promoter.

Conclusions:

  • KDM4C drives TMZ resistance in GBM by epigenetically upregulating E2F6.
  • Targeting KDM4C represents a promising strategy to overcome TMZ resistance in GBM.
  • Combination therapy with KDM4C inhibitors and TMZ may enhance treatment efficacy.
Keywords:
E2F6GlioblastomaKDM4CTMZ resistance

More Related Videos

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

6.8K
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care12:55

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Published on: February 16, 2015

22.0K

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...
5.0K
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...
3.7K
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.
33.4K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K