title: Lactate dehydrogenase downregulation mediates the inhibitory effect of diallyl trisulfide on proliferation, metastasis, and invasion in triple-negative breast cancer.
abstract: The Warburg effect plays a critical role in tumorigenesis, suggesting that specific agents targeting Warburg effect key proteins may be a promising strategy for cancer therapy. Previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of breast cancer cells by inducing apoptosis in vitro and in vivo. However, whether the Warburg effect is involved with the apoptosis-promoting action of DATS is unclear. Here, we show that the action of DATS is associated with downregulation of lactate dehydrogenase A (LDHA), an essential protein of the Warburg effect whose upregulation is closely related to tumorigenesis. Interestingly, inhibition of the Warburg effect by DATS in breast cancer cells did not greatly affect normal cells. Furthermore, DATS inhibited growth of breast cancer cells, particularly in MDA-MB-231, a triple-negative breast cancer (TNBC) cell, and reduced proliferation and migration; invasion was reversed by over-expression of LDHA. These data suggest that DATS inhibits breast cancer growth and aggressiveness through a novel pathway targeting the key enzyme of the Warburg effect. Our study shows that LDHA downregulation is involved in the apoptotic effect of DATS on TNBC. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1390-1398, 2017.
authors: Department of Medical Education and Research and Department of Obstetrics and Gynecology, China Medical University Beigang Hospital, Yunlin, 651, Taiwan, ROC.|Department of Obstetrics and Gynecology, China Medical University An Nan Hospital, Yunlin, 651, Taiwan, ROC.|Obstetrics and Gynecology, School of Medicine, China Medical University, Taichung, Taiwan, 413, Republic of China.
authors: Shi-Yann
authors: SY
authors: Cheng
authors: Departments of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors: Yao-Chih
authors: YC
authors: Yang
authors: Departments of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors: Kuan-Lun
authors: KL
authors: Ting
authors: Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan.|Center for General Education, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
authors: Su-Ying
authors: SY
authors: Wen
authors: Department of Biotechnology, Bharathiar University, Coimbatore, India.
authors: Vijaya Padma
authors: VP
authors: Viswanadha
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung, 404, Taiwan, ROC.|Department of Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan, ROC.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan, ROC.
authors: Chih-Yang
authors: CY
authors: Huang
authors: Departments of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors: Wei-Wen
authors: WW
authors: Kuo
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D050260:Carbohydrate Metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D004794:Enzyme Repression / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D009362:Neoplasm Metastasis; D013440:Sulfides / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D007527:Isoenzymes; D013440:Sulfides; C042577:diallyl trisulfide; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: MDA-MB-231; Warburg effect; apoptosis; diallyl trisulfide; invasion; lactate dehydrogenase A; matrix metallo-proteinase; metastasis; triple negative breast cancer; tumorigenesis