Abstract 85P
Background
The deregulation of epigenetic mechanisms is considered the main agent in the development of GBM. One of the enzymes involved in epigenetic alternation and cancer development are (HDAC) by removal acetyl group from histone and creating condensed chromatin that suppresses transcription gene to histone and non-histone proteins involved in tumorigenesis. Histone deacetylase inhibitors (HADCi) are the most common therapeutic methods for many types of cancer treatments that enabled researchers to study and develop HDAC inhibitors. Mocetinostat, also known as MGCD0103 is an isotype-selective (HDACi) that selectively inhibits HDACs 1−3 and 11 in vitro.
Methods
To demonstrate the role of MGCD0103 to inhibit growth and induce apoptosis in glioblastoma cells. We used different concentrations of MGCD0103 (0.5,1.0,1,5,2.0,2.5) μM on two types of glioblastoma C6 and T98G.
Results
The study showed that MGCD0103 exhibited a potent inhibitory role in the treatment of glioblastoma cancer cells. The MGCD0103103 in a dose- and time-dependent manner are actively contributed to inhibiting cell proliferation, invasion, angiogenesis and induce apoptosis and differentiation through modulating in the molecular mechanism for many pathways inside of cells such as suppression of PI3K/AKT pathway and HDAC1 responsible of many biological processes in cancer initiation and progression, and activation intrinsic and extrinsic pathway involved in apoptosis by upregulating pro-apoptotic proteins BAX and downregulating anti-apoptotic proteins, Bid, Bcl2. Also, the mocetinostat increases the expression of the tumor suppressor gene and decreases the expression of the E2f1 transcription factor. In addition to MGCDO103 induced differentiation by activating differentiation marker GFAP and inhibiting differentiation marker (Id2, N-Myc).
Conclusions
The MGCD0103 is a promising anticancer agent that plays an important role treatment of glioblastoma cells.
Legal entity responsible for the study
F. Khathayer.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.