Abstract

Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM) is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.

Highlights

  • Cancer is the second leading cause of mortality in human diseases worldwide

  • In China, Chinese herbal medicine is widely used as an adjunct therapy to reduce the resistances and side effects of cancer cells to chemotherapy and radiotherapy

  • Many studies have demonstrated an increase in the activities of the glycolytic enzymes such as hexokinase, lactate dehydrogenase A (LDH-A), and glyceraldehydes-3-phosphate dehydrogenase (GAPDH) in various types of tumors and cancer cell lines [47,48,49]

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Summary

Introduction

Cancer is the second leading cause of mortality in human diseases worldwide. According to a national statistic report on the incidence and mortality in the USA, there were a total of 1,529,560 new cancer cases and 569,490 deaths from cancer occurring in 2010 [1]. In China, Chinese herbal medicine is widely used as an adjunct therapy to reduce the resistances and side effects of cancer cells to chemotherapy and radiotherapy. There is an impressive revival of seeking natural lead compounds for the generation of semisynthetic derivatives Current progress in this aspect provide a chemical bank from natural sources for drug discovery and bring better understanding for the chemical basis of Chinese herbal medicine for cancer treatment. TCM formulas and therapies are generally considered to regulate multiple cellular signal pathways [16] Herbal medicine and their active components are promising sources for the designs of more effective and less toxic agents in cancer chemoprevention and treatment [17]. In the present paper, we intend to review current progress about TCM-derived phytochemicals which target the key enzymes and proteins involved in cancer glycolysis

Glycolytic Pathway as a Target for Cancer Therapy
Glycolytic Molecular Targets and Herb-derived Inhibitors
Perspectives
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