Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine
2006

Overcoming Cancer Drug Resistance with Hydralazine

publication Evidence: moderate

Author Information

Author(s): Segura-Pacheco Blanca, Perez-Cardenas Enrique, Taja-Chayeb Lucia, Chavez-Blanco Alma, Revilla-Vazquez Alma, Benitez-Bribiesca Luis, Duenas-Gonzalez Alfonso

Primary Institution: Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autonóma de Mexico

Hypothesis

Can DNA hypermethylation contribute to chemotherapy resistance in cancer cells, and can it be reversed by demethylating agents?

Conclusion

DNA hypermethylation contributes to the development of multidrug resistance in cancer cells, and hydralazine can reverse this resistance.

Supporting Evidence

  • MCF-7/Adr cells showed increased DNA hypermethylation compared to wild-type MCF-7 cells.
  • Hydralazine treatment restored adriamycin sensitivity in MCF-7/Adr cells.
  • DNA methyltransferase activity was higher in resistant cells, indicating a role in drug resistance.
  • Antisense targeting of dnmt genes reduced methylation and increased drug sensitivity.

Takeaway

Some cancer cells become resistant to treatment because of changes in their DNA. A medicine called hydralazine can help make these cells sensitive to treatment again.

Methodology

MCF-7 cells were treated with adriamycin to induce resistance, and then analyzed for DNA methylation and drug sensitivity after treatment with hydralazine.

Limitations

The study primarily focuses on a single cell line model, which may not fully represent all cancer types.

Digital Object Identifier (DOI)

10.1186/1479-5876-4-32

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