Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) Coordinately Modulates Cell Cycle Regulatory Genes and Intrinsic and Extrinsic Apoptotic Pathway Genes to Induce Apoptosis in Human Glioblastoma, Medulloblastoma, and Acute Lymphoblastic Leukemia Cells.

Background: Cell cycle progression is regulated by coordinated interplay among cyclin-dependent kinases (CDKs), cyclins, and cyclin-dependent kinase inhibitors (CKIs). In many human cancers, CKIs are epigenetically silenced through promoter hypermethylation and histone deacetylation, contributing to uncontrolled cell proliferation and impaired apoptosis. Restoration of histone acetylation by histone deacetylase inhibitors (HDACIs) promotes the re-expression of epigenetically silenced tumor suppressor genes, thereby modulating cell cycle control and apoptotic pathways. Building on our previous findings with trichostatin A (TSA), the present study evaluated vorinostat (suberoylanilide hydroxamic acid, SAHA) in three human cancer cell lines. Objectives: To evaluate the effects of SAHA on the expression of genes involved in cell cycle regulation and in the intrinsic and extrinsic apoptotic pathways, and to assess its ability to induce apoptosis in glioblastoma, medulloblastoma, and acute lymphoblastic leukemia cell lines. Methods: Half-maximal inhibitory concentration (IC Results: SAHA significantly modulated the expression of most cell cycle regulatory genes and genes involved in the intrinsic and extrinsic apoptotic pathways. These molecular alterations were accompanied by a significant increase in apoptosis across all three cancer cell lines. Conclusions: SAHA promotes apoptosis by modulating the expression of cell cycle regulatory genes and activating both extrinsic and intrinsic apoptotic pathways, highlighting its potential as an epigenetic therapeutic agent for glioblastoma, medulloblastoma, and acute lymphoblastic leukemia.