HDAC4 Degradation by Combined TRAIL and Valproic Acid Treatment Induces Apoptotic Cell Death of TRAIL-resistant Head and Neck Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2018 Aug 23

PMID 30131570

Citations 12

Authors

Bok-Soon Lee

Yeon Soo Kim

Haeng-Jun Kim

Dae-Ho Kim

Ho-Ryun Won

Yong-Sung Kim

Chul-Ho Kim

Affiliations

Soon will be listed here.

Abstract

Although TRAIL can directly induce cell death in some cancer cells, it appears that TRAIL resistance exists in many cancers. This study focuses on anti-cancer drugs for TRAIL-resistant head and neck cancer (HNC) to provide further progress toward effective cancer therapy. Results indicate in TRAIL-resistant HNC cells, that combined TRAIL and VPA treatment greatly reduced cell viability and therefore induced cell death, relative to treatment with TRAIL or VPA alone. A caspase-dependent signaling pathway was demonstrated, and combined treatment with TRAIL and VPA also significantly decreased the expression of HDAC4. When we pretreated cells with z-VAD followed by combined treatment with TRAIL and VPA, cell death was blocked with no reduction in expression of HDAC4. To confirm that cell death involved HDAC4 in HNC cells, we knocked down expression of HDAC4 with siRNA, followed by treatment with TRAIL and VPA. Results showed that loss of HDAC4 sensitized the TRAIL-resistant HNC cells to apoptotic cell death. Finally, we showed elevated expression of HDAC4 in HNC tissues compared to normal tissues obtained from the same patients. In conclusion, we suggest that combined VPA and TRAIL treatment may be a promising therapy for HNC via HDAC4 degradation.

Citing Articles

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PMID: 39090444 DOI: 10.1007/s10620-024-08569-5.

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Synergistic Interaction of the Class IIa HDAC Inhibitor CHDI0039 with Bortezomib in Head and Neck Cancer Cells.

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Cuttini E, Goi C, Pellarin E, Vida R, Brancolini C Front Mol Biosci. 2023; 10:1116660.

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