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: Shi-Yann Cheng, Yao-Chih Yang, Kuan-Lun Ting, Su-Ying Wen, Vijaya Padma Viswanadha, Chih-Yang Huang, Wei-Wen Kuo
• Journal: Environmental toxicology (Environ Toxicol) Vol. 32 Issue 4 Pg. 1390-1398 (Apr 2017) ISSN: 1522-7278 [Electronic] United States
• PMID: 27566995 (Publication Type: Journal Article)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Allyl Compounds
• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Isoenzymes
• Sulfides
• diallyl trisulfide
• L-Lactate Dehydrogenase
• Lactate Dehydrogenase 5

Topics

• Allyl Compounds (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins
• Carbohydrate Metabolism
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival
• Down-Regulation
• Drug Screening Assays, Antitumor
• Enzyme Repression (drug effects)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Isoenzymes (genetics, metabolism)
• L-Lactate Dehydrogenase (genetics, metabolism)
• Lactate Dehydrogenase 5
• Neoplasm Metastasis
• Sulfides (pharmacology)
• Triple Negative Breast Neoplasms (drug therapy, enzymology, pathology)