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Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death.
MedLine Citation:
PMID:  22190257     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Solid tumors are dependent on glucose, but are generally glucose-deprived due to poor vascularization. Nevertheless cancer cells can generally survive glucose deprivation better than their normal counterparts. Thus, to render cancer cells sensitive to glucose depletion may potentially provide an effective strategy for cancer intervention. We propose that lactic acidosis, a tumor microenvironment factor, may allow cancer cells to develop a resistance to glucose deprivation-induced death, and that disruption of lactic acidosis may resume cancer cells' sensitivity to glucose depletion. Lactic acidosis, lactosis, or acidosis was generated by adding pure lactic acid, sodium lactate, or HCl to the culture medium. Cell death, cell cycle, autophagy, apoptosis and gene expression profiling of the survived cancer cells under glucose deprivation with lactic acidosis were determined. Under glucose deprivation without lactic acidosis, 90% 4T1 cancer cells died within a single day; in a sharp contrast, under lactic acidosis, 90% 4T1 cells died in a period of 10 days with viable cells identified even 65 days after glucose was depleted. Upon glucose restoration, survived cells resumed proliferation. Lactic acidosis also significantly extended survival of other cancer cells under glucose deprivation. G1/G0 arrest, autophagy induction, and apoptosis inhibition were tightly associated with lactic acidosis-mediated resistance to glucose deprivation. Lactosis alone had no effect on cell survival under glucose deprivation; acidosis alone can prolong cell survival time but not as potent as lactic acidosis. Thus, the ability of cancer cells to resist glucose deprivation-induced cell death is conferred, at least in part, by lactic acidosis, and we envision that disrupting the lactic acidosis may resume the sensitivity of cancer cells to glucose deprivation. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors:
Hao Wu; Zonghui Ding; Danqing Hu; Feifei Sun; Chunyan Dai; Jiansheng Xie; Xun Hu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-21
Journal Detail:
Title:  The Journal of pathology     Volume:  -     ISSN:  1096-9896     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Affiliation:
Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine.
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