Topics in Anti-Cancer Research

Volume: 6

Regulation/Inhibition of Human Lactate Dehydrogenase A: An Innovative and Potential Approach for Anti-Cancer Drugs Development

Author(s): Vinit Kumar, Atul Kumar and Reshma Rani

Pp: 114-142 (29)

Doi: 10.2174/9781681084558117060008

* (Excluding Mailing and Handling)

Abstract

Human lactate dehydrogenase (hLDH-A), a glycolytic enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD+, plays a crucial role in the promotion of glycolysis in invasive tumor cells. hLDH-A has been considered a vital therapeutic target for invasive cancers therefore, hLDH-A inhibition reflects a valuable attempt in the development of innovative anticancer strategies. Reagents that regulate or inhibit hLDH-A enzyme/ gene can play a role in the prevention and treatment of various cancers and related diseases. In fact, selective inhibition of hLDH-A using small molecules holds potential prospects for the treatment of cancer. Consequently, significant progress has been made in the discovery of smallmolecules, the selective inhibitors of hLDH-A displaying remarkable inhibitory potency. The LDH-based approaches in the development of anticancer therapy and treatment of related diseases are worthwhile because of the existence of LDH enzyme at the end of glycolytic pathway. In this book chapter, 59 review and research articles, and 15 patents filed on LDH and its application are discussed. Latest contributions in regulation/inhibition of the LDH-A enzyme by various agents are summarized in this book chapter.


Keywords: Aerobic glycolysis, anaerobic glycolysis, anti-inflammatory activity, anti-proliferative activity, cancer cell metabolism, cancer cell proliferation, epileptic treatment, FDG-PET, FRET, glycolytic pathway, gossypol, human lactate dehydrogenase A, human lactate dehydrogenase B, isostere of pyruvate, metabolic switch, mitochondrial dysfunction, NADH/NAD+, nanosensor, Nhydroxy- indole, pyruvate dehydrogenase complex, selective hLDH5 inhibitors, tumor glycolysis, warburg effect.

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