Effects of caffeine on cell viability and activity of histone deacetylase 1 and histone acetyltransferase in glioma cell

Jin-Cherng Chen^{a, b,} Juen-Haur Hwang^{b, c, d,} 

^a Department of Neurosurgery, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
^b School of Medicine, Tzu Chi University, Hualien, Taiwan
^c Department of Otolaryngology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
^d Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan

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Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation

Abstract

Objective

The prognosis of patients with glioblastoma remains poor even after various treatments such as surgery, radiotherapy, and chemotherapy. Thus, development of new drugs is urgently needed. The mechanisms underlying the cytotoxicity of caffeine in glioma cells are not clearly understood. This study aimed to assess the activities of histone deacetylase 1 (HDAC1) and histone acetyltransferase (p300) in RT2 glioma cells treated with caffeine.

Materials and Methods

Cell viability and activity of HDAC1 and p300 in RT2 glioma cells were assayed after treatment with caffeine for 48 hours.

Results

Cell viability decreased significantly after treatment with 0.5mM, 1mM, and 2mM caffeine. HDAC1 protein activity decreased significantly with various concentrations of caffeine, whereas the activity of p300 increased significantly. In addition, the viability of RT2 cells remained high, but HDAC1 activity decreased, and p300 activity increased markedly with 0.5mM caffeine treatment. We used microRNA and small interfering RNA (siRNA) to regulate HDAC1 and p300 to further understand the impact on glioblastomas. siRNA downregulated p300 and thus increased the viability of RT2 cells, therefore, caffeine combined with siRNA abolished the efficacy of caffeine, which confirmed that caffeine upregulated p300 and reduced cell viability. We also found increased HDAC1 activity when RT2 cells were treated with a combination of caffeine and miR-449a and thus increased the viability of RT2 cells.

Conclusion

Our data suggest that a new strategy, caffeine, could increase glioma cell death by decreasing HDAC1 activity and/or by increasing p300 activity. The changes in HDAC1 and p300 activities appeared to occur earlier than loss of RT2 cells.

Keywords

Caffeine; Glioma cells; Histone acetyltransferase; Histone deacetylase 1; p300