Valproic Acid Represses Autophagy and Enhances the Anti-myeloma Activity of DNA-damaging Drugs

To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism. Human multiple myeloma(MM) cells were treated with VPA of non-toxic dose in absence and presence of DOX or MEL at different concentrations (ie. IC10, IC20, IC40). The...

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Published inZhongguo shi yan xue ye xue za zhi Vol. 23; no. 3; p. 718
Main Authors Jin, Yu-Long, Dong, Bao-Xia, Xu, Li, Tang, Hai-Long, Gao, Guang-Xun, Gu, Hong-Tao, Shu, Mi-Mi, Chen, Xie-Qun
Format Journal Article
LanguageChinese
Published China 01.06.2015
Subjects
Acetylation
Autophagy
Cell Line, Tumor
Cell Proliferation
DNA
DNA Damage
Doxorubicin
Humans
Multiple Myeloma
Valproic Acid
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Summary:To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism. Human multiple myeloma(MM) cells were treated with VPA of non-toxic dose in absence and presence of DOX or MEL at different concentrations (ie. IC10, IC20, IC40). The cell proliferation was detected by MTT method. Western blot was used to detect the expression levels of autophagy-related proteins (LC3, ATG5, ATG7) and acetylated histone H4K16ac. Cell proliferation inhibition markedly increased in VPA plus DOX or MEL as compared with DOX or MEL alone (P<0.05). Both LC3 and H4K16ac expression levels in co-treatment were between VPA and DOX or MEL treated alone. Importantly, VPA of non-toxic dose not only augmented the anti-myeloma activity of DOX or MEL, but also down-regulated the autophagy-related protein expression and increases H4K16ac protein levels. H4K16ac can inhibit the transcription of autophagy-related genes, The VPA enhance the anti-myeloma activity of DNA-damaging dr
ISSN:1009-2137
DOI:10.7534/j.issn.1009-2137.2015.03.023