Open AccessHDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation and inhibits telomerase activity
Author(s) -
Sharma Vivek,
Koul Nitin,
Joseph Christy,
Dixit Deobrat,
Ghosh Sadashib,
Sen Ellora
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00844.x
Subject(s) - apoptosis , telomerase , transfection , histone deacetylase inhibitor , glioma , cancer research , cell culture , microbiology and biotechnology , kinase , chemistry , histone deacetylase , biology , histone , dna , biochemistry , genetics , gene
The present study identified a novel mechanism of induction of apoptosis in glioblastoma cells by scriptaid – a histone deacetylase (HDAC) inhibitor. Scriptaid reduced glioma cell viability by increasing Jun N‐terminal kinase (JNK) activation. Although scriptaid induced activation of both p38MAPK and JNK, it was the inhibition of JNK that attenuated scriptaid‐induced apoptosis significantly. Scriptaid also increased the expression of ( i ) p21 and p27 involved in cell‐cycle regulation and ( ii ) γH2AX associated with DNA damage response in a JNK‐dependent manner. Treatment with scriptaid increased Ras activity in glioma cells, and transfection of cells with constitutively active RasV12 further sensitized glioma cells to scriptaid‐induced apoptosis. Scriptaid also inhibited telomerase activity independent of JNK. Taken together, our findings indicate that scriptaid ( i ) induces apoptosis and reduces glioma cell proliferation by elevating JNK activation and ( ii ) also decreases telomerase activity in a JNK‐independent manner.