Role of class I and class II histone deacetylases in carcinoma cells using siRNA.
The role of the individual histone deacetylases (HDACs) in the regulation of cancer cell proliferation was investigated using siRNA-mediated protein knockdown. The siRNA for HDAC3 and HDAC1 demonstrated significant morphological changes in HeLa S3 consistent with those observed with HDAC inhibitors. SiRNA for HDAC 4 or 7 produced no morphological changes in HeLa S3 cells. HDAC1 and 3 siRNA produced a concentration-dependent inhibition of HeLa cell proliferation; whereas, HDAC4 and 7 siRNA showed no effect. HDAC3 siRNA caused histone hyperacetylation and increased the percent of apoptotic cells. These results demonstrate that the Class I HDACs such as HDACs 1 and 3 are important in the regulation of proliferation and survival in cancer cells. These results and the positive preclinical results with non-specific inhibitors of the HDAC enzymes provide further support for the development of Class I selective HDAC inhibitors as cancer therapeutics.
Glaser
Keith B
KB
Cancer Research, R47J-AP9, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6121, USA. keith.glaser@abbott.com
Li
Junling
J
Staver
Michael J
MJ
Wei
Ru-Qi
RQ
Albert
Daniel H
DH
Davidsen
Steven K
SK
D000107:Acetylation; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
D000970:Antineoplastic Agents; D006657:Histones; D034741:RNA, Small Interfering; D006655:Histone Deacetylases