Natural compounds targeting mitochondrial metabolism in cancer therapy: a literature review

Cancer is a public health problem and is considered the leading cause of death around the globe. Despite the advances in cancer therapies, many patients suffer from adverse side effects and drug resistance. Among the cancer hallmarks, metabolic reprogramming is essential for supporting the higher energy demand of cancer cells. Due to the Warburg effect, a misconception that oxidative phosphorylation (OXPHOS) and other mitochondrial-related metabolic pathways are dispensable for tumor cells was created. Nowadays, many studies have been demonstrating the importance of mitochondria and their metabolism to cancer bioenergetics and progression. Through this review, we aim to show natural compounds that regulate mitochondrial metabolism to exert their anticancer activity.

In this literature review, studies found in PubMed, in English and published between 1925-2025 were considered.

Throughout this review, we discussed the importance of mitochondrial metabolism for carcinogenesis, updated and brought new natural products as potential therapies to target mitochondrial metabolism to counteract cancer progression. Furthermore, we discussed the future directions to overcome the limitations of the use of natural products as anticancer compounds.

Natural compounds can act in different pathways of mitochondrial metabolism to exert their antitumoral effects, however, some limitations need to be overcome. Developing natural product-based hybrids through the conjugation of natural compounds with bioactive molecules has gained interest to surpass these limitations, representing a good strategy to enhance the anticancer treatment effectiveness of natural products.