Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy

Cancer Science
Zijun ZhenYoujian He

Abstract

Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to pacli...Continue Reading

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Citations

Aug 22, 2018·British Journal of Pharmacology·Belén Espinosa, Elias S J Arnér
Feb 6, 2019·International Journal of Molecular Medicine·Cheng-Lin WuLi-Jun Zhou
Jan 7, 2021·Cancer Metastasis Reviews·Irfete S Fetahu, Sabine Taschner-Mandl
Feb 13, 2021·International Journal of Molecular Sciences·Hye In KimBo Hyon Yun
Mar 16, 2021·Frontiers in Oncology·Malina XiaoBassam Janji
Jun 3, 2021·Journal of Personalized Medicine·Jeremy Z R HanDavid R Croucher

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Methods Mentioned

BETA
confocal microscopy
transfection
transmission electron microscopy
flow cytometry
acetylation

Software Mentioned

SPSS
MetaMorph offline

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