Many pathways of energy metabolism exist in cancer, including glycolysis, amino acid metabolism, fatty acid oxidation, and mitochondrial respiration. Cancer cells mainly generate energy through glycolysis to sustain cancer cell growth and biosynthesis under aerobic conditions.

Natural products regulate many steps in glycolysis, and targeting glycolysis using natural products is a promising approach to cancer therapy. Natural products, such as resveratrol, licochalcone A from Glycyrrhiza inflate and many others may affect glycolysis pathways in cancer by targeting glycolytic enzymes, proteins, oncogenes and glycolytic signaling proteins.

Glycolysis by targeting natural products can effectively inhibit tumor growth and provide an approach to effectively treat various cancers. As for the tumor itself, cancer cells in a nutrient-rich environment show little or no sensitivity to targeted metabolic inhibitors. Tumors may cleverly use their environment to boost their metabolism, providing the basis for escape.

by the immune system.

However, high glycolytic flux depends on glycolysis-related genes and its targeting is beneficial for tumor therapy. Metabolic reprogramming is a central feature of cancer and is critical for tumorigenesis and tumor progression

Natural products can inhibit the MYC proto-oncogene, which ultimately suppresses HIF-1α-induced metabolic reprogramming toward a glycolytic phenotype. Natural products have advantages in improving the metabolic reprogramming of cancer cells with their polypharmacological actions. In the glycolysis signaling pathway, AMPK activation and PI3K/AKT/mTOR inhibition are the main targets of these products.

More and more bioactive drugs have been shown to be widely used as adjuvant therapy after surgery, chemotherapy, radiotherapy or other

types of cancer therapy, alleviating various side effects caused by chemotherapy, such as gene mutation, cytotoxicity and drug resistance, showing promising therapeutic effects in clinical treatment. Compared to chemotherapy, natural products have the advantage of availability, high efficacy and low toxicity. Continued investigation of the effective targets of natural products in glycolysis is needed to gain a more complete picture of the mechanisms involved and potential therapeutic targets However, “natural” is not equivalent to “safe” and toxicity still seriously hinders widespread use of natural products.

SOURCE: Pharmacol 2022