Terpenoids: Unlocking Their Potential on Cancer Glucose Metabolism.

Abstract

Cancer incidence has increased globally and has become the leading cause of death in the majority of countries. Many cancers have altered energy metabolism pathways, such as increased glucose uptake and glycolysis, as well as decreased oxidative phosphorylation. This is known as the Warburg effect, where cancer cells become more reliant on glucose to generate energy and produce lactate as an end product, even when oxygen is present. These are attributed to the overexpression of key glycolytic enzymes, glucose transporters, and related signaling pathways that occur in cancer cells. Therefore, overcoming metabolic alterations in cancer cells has recently become a target for therapeutic approaches. Natural products have played a key role in drug discovery, especially for cancer and infectious diseases. In this review, we are going to focus on terpenoids, which are gradually gaining popularity among drug researchers due to their reported anti-cancer effects via cell cycle arrest, induction of apoptosis, reduction of proliferation, and metastasis. This review summarizes the potential of 13 terpenoid compounds as anti-glycolytic inhibitors in different cancer models, primarily by inhibiting the glucose uptake and the generation of lactate, as well as by downregulating enzymes associated to glycolysis. As a conclusion, disruption of cancer cell glycolysis may be responsible for the anti-cancer activity of terpenoids.