Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells.
Acetylation of histones and nonhistone proteins is an important post-translational modification involved in the regulation of gene expression in mammalian cells. Dysfunction of histone acetyltransferase (HAT) is often associated with the manifestation of several diseases. In this report, HATs are new targets for the development of therapeutics. Our studies first proved that curcumin induces histone hypoacetylation in brain cancer cells and finally induces apoptotic cell death through a (PARP)- and caspase 3-mediated manner. In addition, curcumin induces recontrolling of neural stem cell fates. It induces effective neurogenesis, synaptogenesis, and migration of neural progenitor cells in vitro in brain-derived adult neural stem cells. We also confirmed the neurogenic effect of curcumin in our in vivo experiments. Curcumin actively suppressed differentiation in astrocytes while promoting differentiation into the neurons associated with decrease of histone H3 and H4 acetylation. We suggest that histone hypoacetylation plays an important role in determine stem cell fate through controlling the simultaneous expression of many genes. Thus, the present finding that curcumin, a nontoxic dietary compound, is a histone acetyltransferase inhibitor would supply a new window to understand further the molecular mechanism of histone acetylase inhibitors (HAI) in cancer and neural stem cells and provide a new target molecule for treating central nervous system disorders.
Kang
Soo-Kyung
SK
Department of Physiology, College of Medicine, Pusan National University, Busan, South Korea. skkang@pusan.ac.kr
Cha
Seung-Heun
SH
Jeon
Hyo-Gon
HG
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024161:Collagen Type XI / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D006657:Histones; D051028:bcl-2-Associated X Protein; D051548:Histone Acetyltransferases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin