| Literature DB >> 26735433 |
Meng-Meng Ji1, Li Wang1,2, Qin Zhan2, Wen Xue1, Yan Zhao1, Xia Zhao1,2, Peng-Peng Xu1, Yang Shen1, Han Liu1, Anne Janin2,3, Shu Cheng1, Wei-Li Zhao1,2.
Abstract
Autophagy is closely related to tumor cell sensitivity to anticancer drugs. The HDAC (histone deacetylase) inhibitor valproic acid (VPA) interacted synergistically with chemotherapeutic agents to trigger lymphoma cell autophagy, which resulted from activation of AMPK (AMP-activated protein kinase) and inhibition of downstream MTOR (mechanistic target of rapamycin [serine/threonine kinase]) signaling. In an HDAC-independent manner, VPA potentiated the effect of doxorubicin on lymphoma cell autophagy via reduction of cellular inositol 1,4,5 trisphosphate (IP3), blockade of calcium into mitochondria and modulation of PRKAA1/2-MTOR cascade. In murine xenograft models established with subcutaneous injection of lymphoma cells, dual treatment of VPA and doxorubicin initiated IP3-mediated calcium depletion and PRKAA1/2 activation, induced in situ autophagy and efficiently retarded tumor growth. Aberrant genes involving mitochondrial calcium transfer were frequently observed in primary tumors of lymphoma patients. Collectively, these findings suggested an HDAC-independent chemosensitizing activity of VPA and provided an insight into the clinical application of targeting autophagy in the treatment of lymphoma.Entities:
Keywords: AMP-activated; autophagy; catalytic subunit; chemosensitivity; histone deacetylase inhibitor; inositol 1,4,5 trisphosphate; lymphoma; protein kinase; valproic acid; α
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Year: 2015 PMID： 26735433 PMCID： PMC4835147 DOI： 10.1080/15548627.2015.1082024
Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 16.016