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DNA demethylation

Sunday 17 April 2011

Demethylation

Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in cancer therapy.

Statins are cholesterol-lowering drugs with an excellent safety profile and associated with a reduced incidence of various cancers including colorectal cancer (CRC).

Statins act by activating tumour suppressive bone morphogenetic protein (BMPs) signalling (BMPs signaling) in CRC, increasing expression of BMP2. BMP2 is silenced by hypermethylation in gastric cancer.

Statins act as DNMT inhibitors, demethylating the BMP2 promoter, activating BMP signalling, inducing differentiation of CRC cells, and reducing ’stemness’.

This study indicates that statins may be able to be used as differentiating agents in combined or adjuvant therapy in CRC with the CpG island methylator phenotype.

See also

- DNA hypermethylation
- statins

References

- Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ’stemness’ via the bone morphogenetic protein pathway (BMPs). Kodach LL, Jacobs RJ, Voorneveld PW, Wildenberg ME, Verspaget HW, van Wezel T, Morreau H, Hommes DW, Peppelenbosch MP, van den Brink GR, Hardwick JC. Gut. 2011 Nov;60(11):1544-53. PMID: 21551187

- Epigenetics: Demethylation links cell fate and cancer. Swami M. Nat Rev Genet. 2010 Nov;11(11):749. PMID: 20921960