期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 133, 期 4, 页码 176-185出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2012.01.008
关键词
Retinoic acid; Neuroblastoma; Glycolysis; Oxidative phosphorylation
资金
- NCI NIH HHS [P01 CA092584] Funding Source: Medline
- NIEHS NIH HHS [R01 ES020766] Funding Source: Medline
- NINDS NIH HHS [R01 NS060115-01, R01 NS040738, RC1 NS069177-02, R01 NS062384, NS060115, RC1 NS069177-01, R01 NS060115, RC1 NS069177, R01 NS062384-02, NS069177, NS40738, NS062384] Funding Source: Medline
Retinoic acid (RA) is used in differentiation therapy to treat a variety of cancers including neuroblastoma. The contributing factors for its therapeutic efficacy are poorly understood. However, mitochondria (MT) have been implicated as key effectors in RA-mediated differentiation process. Here we utilize the SH-SY5Y human neuroblastoma cell line as a model to examine how RA influences MT during the differentiation process. We find that RA confers an approximately sixfold increase in the oxygen consumption rate while the rate of glycolysis modestly increases. RA treatment does not increase the number of MT or cause measurable changes in the composition of the electron transport chain. Rather, RA treatment significantly increases the mitochondrial spare respiratory capacity. We propose a competition model for the therapeutic effects of RA. Specifically, the high metabolic rate in differentiated cells limits the availability of metabolic nutrients for use by the undifferentiated cells and suppresses their growth. Thus. RA treatment provides a selective advantage for the differentiated state. Published by Elsevier Ireland Ltd.
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