title: Different effects of LDH-A inhibition by oxamate in non-small cell lung cancer cells.
abstract: Higher rate of glycolysis has been long observed in cancer cells, as a vital enzyme in glycolysis, lactate dehydrogenase A (LDH-A) has been shown with great potential as an anti-cancer target. Accumulating evidence indicates that inhibition of LDH-A induces apoptosis mediated by oxidative stress in cancer cells. To date, it's still unclear that whether autophagy can be induced by LDH-A inhibition. Here, we investigated the effects of oxamate, one classic inhibitor of LDH-A in non-small cell lung cancer (NSCLC) cells as well as normal lung epithelial cells. The results showed that oxamate significantly suppressed the proliferation of NSCLC cells, while it exerted a much lower toxicity in normal cells. As previous studies reported, LDH-A inhibition resulted in ATP reduction and ROS (reactive oxygen species) burst in cancer cells, which lead to apoptosis and G2/M arrest in H1395 cells. However, when being exposed to oxamate, A549 cells underwent autophagy as a protective mechanism against apoptosis. Furthermore, we found evidence that LDH-A inhibition induced G0/G1 arrest dependent on the activation of GSK-3β in A549 cells. Taken together, our results provide useful clues for targeting LDH-A in NSCLC treatment and shed light on the discovery of molecular predictors for the sensitivity of LDH-A inhibitors.
authors.affiliation: Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou, China. Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China. School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wan
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China. Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou, China. Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010072:Oxamic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D010072:Oxamic Acid