Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response

Dong,Xiaoxian; Liao,Yuning; Liu,Ningning; Hua,Xianliang; Cai,Jianyu; Liu,Jinbao; Huang,Hongbiao

doi:10.3892/mmr.2016.5533

Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response

Authors:
- Xiaoxian Dong
- Yuning Liao
- Ningning Liu
- Xianliang Hua
- Jianyu Cai
- Jinbao Liu
- Hongbiao Huang
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Affiliations: Protein Modification and Degradation Laboratory, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China
Published online on: July 19, 2016 https://doi.org/10.3892/mmr.2016.5533
Pages: 2679-2684

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Abstract

Bortezomib (Bor), a proteasome inhibitor, has marked therapeutic effects in multiple myeloma (MM), and its synergistic effects with other anticancer agents have been widely investigated. In the present study, endoplasmic reticulum (ER) stress was the target of the treatment strategy; anacardic acid (AA) and Bor induce ER stress, resulting in apoptosis of multiple myeloma cells. AA/Bor combination therapy exhibited overt cytotoxicity in MM cells, by synergistically reducing cell growth and promoting cell death. Notably, expression levels of the stress‑associated molecules binding protein, phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4 (ATF4) and CCAAT‑enhancer binding protein homologous protein (CHOP) were increased following treatment. AA/Bor combination therapy‑induced U266 cell cytotoxicity was partially reversed by ATF4 gene silencing and slightly enhanced by CHOP knockdown. The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment.

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