Combined Inhibition of HDAC and EGFR Reduces Viability and Proliferation and Enhances STAT3 mRNA Expression in Glioblastoma Cells.

Abstract

Changes in expression of histone deacetylases (HDACs), which epigenetically regulate chromatin structure, and mutations and amplifications of the EGFR gene, which codes for the epidermal growth factor receptor (EGFR), have been reported in glioblastoma (GBM), the most common and malignant type of brain tumor. There are likely interplays between HDACs and EGFR in promoting GBM progression, and HDAC inhibition can cooperate with EGFR blockade in reducing the growth of lung cancer cells. Here, we found that either HDAC or EGFR inhibitors dose-dependently reduced the viability of U87 and A-172 human GBM cells. In U87 cells, the combined inhibition of HDACs and EGFR was more effective than inhibiting either target alone in reducing viability and long-term proliferation. In addition, HDAC or EGFR inhibition, alone or combined, led to G0/G1 cell cycle arrest. The EGFR inhibitor alone or combined with HDAC inhibition increased mRNA expression of the signal transducer and activator of transcription 3 (STAT3), which can act either as an oncogene or a tumor suppressor in GBM. These data provide early evidence that combining HDAC and EGFR inhibition may be an effective strategy to reduce GBM growth, through a mechanism possibly involving STAT3.

• Authors: Marienela Buendia Duque, Kelly de Vargas Pinheiro, Amanda Thomaz, Camila Alves da Silva, Natália Hogetop Freire, André Tesainer Brunetto, Gilberto Schwartsmann, Mariane Jaeger, Caroline Brunetto de Farias, Rafael Roesler
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 68 Issue 1 Pg. 49-57 (May 2019) ISSN: 1559-1166 [Electronic] United States
• PMID: 30887411 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• RNA, Messenger
• STAT3 Transcription Factor
• STAT3 protein, human
• ErbB Receptors

Topics

• Antineoplastic Agents (pharmacology)
• Brain Neoplasms (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• ErbB Receptors (antagonists & inhibitors)
• Glioblastoma (metabolism)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• RNA, Messenger (genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)