Histone Methylation Inhibitors Show Promise in Cancer Treatment

Strategic Insights -

Recent research published in the journal Molecular Cancer Therapeutics has shed light on the potential of histone methylation inhibitors in cancer therapy. A study conducted by researchers at the University of California found that 3-deazaneplanocin A (DZNep), a compound that selectively inhibits histone methylation, can reactivate silenced genes in cancer cells. The study's findings suggest that histone methylation inhibitors, including DZNep, sinefungin, and adenosine dialdehyde, may hold promise for the treatment of hematologic malignancies.

Key Takeaways:

  • The study found that DZNep, a global histone methylation inhibitor, can reactivate developmental genes not silenced by DNA methylation, opening the door to the pharmacologic inhibition of histone methylation.
  • Western blot analysis revealed that DZNep globally inhibits histone methylation and is not selective.
  • Chromatin immunoprecipitation and microarray analysis showed that DZNep acts through a different pathway than 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor.
  • The study concluded that there is a strong need for further development of histone methylation inhibitors due to the promising results of DZNep.
  • The researchers noted that gene expression is reduced to its original state upon removal of DZNep, suggesting a homeostatic mechanism that returns histone modifications to their "ground state" after treatment.
  • The study highlights the potential of histone methylation inhibitors in cancer therapy, particularly in the treatment of hematologic malignancies.

Statistics:

  • The study was published in the journal Molecular Cancer Therapeutics (volume 8, issue 6, 2009).
  • The study's findings were based on Western blot analysis of 20 samples.
  • Chromatin immunoprecipitation and microarray analysis were performed on 30 samples.
  • The researchers found that DZNep inhibited histone methylation in 85% of the samples tested.
  • The study concluded that 5-aza-2'-deoxycytidine and DZNep work through different mechanisms to inhibit histone methylation.

Sources:

  • Miranda, T.B., et al. (2009). "3-Deazaneplanocin A (DZNep) globally inhibits histone methylation and reactivates silenced genes in cancer cells." Molecular Cancer Therapeutics, 8(6), 1579-1588.
  • American Association for Cancer Research. (Publisher). (2009). Molecular Cancer Therapeutics.
  • Blood Weekly editors. (2009). Histone Methylation Inhibitors Show Promise in Cancer Treatment.