Nature's Cancer Combatants: Bioactive Compounds Disrupting Tumour Metabolism

Abstract

Metabolic reprogramming in cancer cells has been well-characterised as a hallmark of tumorigenesis and therapeutic resistance. Cancer cells exhibit enhanced glycolysis, glutaminolysis, dysregulated oxidative phosphorylation (OXPHOS), and aberrant lipid metabolism to support their rapid proliferation and survival under various unfavourable conditions. Natural products are one of the richest pools for potentially disrupting numerous metabolic pathways, and thus modulating these routes has recently come to light as a new cancer treatment strategy. This chapter is a comprehensive and systematic review of the evidence published in the last 20 years, about natural chemicals and cancer metabolism. Investigation on natural substances such as resveratrol, curcumin, berberine, quercetin and epigallocatechin gallate (EGCG) is being extensively conducted with the potential to modify key metabolic pathways implicated in cancer metastasis.  The efficacy of these molecules comes from the ability to target glycolytic enzymes (e.g., pyruvate kinase M2 (PKM2), hexokinase 2 (HK2)), lipid biosynthesis (fatty acid synthase [FASN], stearoyl-CoA desaturase 1[SCD1]), oxidative phosphorylation and mitochondria function, and glutaminolysis through glutamine utilization. The work of this article was used extensively for those mechanistic experiments of this research paper such as a Western Blot, Enzymatic Test, Metabolomic Profiling and Mitochondrial Function. The findings reveal that natural products help inhibit tumour growth and enhance the response of cancer cells to radiation and chemotherapy, without induced relapse. While promising, there is still work to be done before these preclinical results can be translated into a clinical setting, primarily because each cancer has a unique tumour metabolism and the possibility of off-target effects remains concerning. However, the promise of natural chemicals as future therapeutic agents in cancer treatment is highlighted by their capacity to influence diverse metabolic pathways and reduce toxicity profiles. More clinical research and dose strategy optimisation is essential to reap the benefits of these natural substances fully.