Antitumoral Effects of Fungal Natural Products on Chronic Myeloid Leukemia Models: What Do We Know so Far?

CML is a myeloproliferative disease related to several cases of resistance and intolerance to treatments; therefore, the search for new therapeutic agents in natural products has become increasingly important. The chemical diversity and bioactive structures among fungal secondary metabolites (FSM) are enormous and still little explored as potential antileukemic drugs. Thus, the objective of this review is to provide information on articles in the literature that used FSM as agents against CML and to discuss them critically to direct new studies against this disease. We analyzed 26 scientific articles published in the last 20 years that identified or did not identify the main mechanism of action in the form of either an isolated compound or a complex extract in CML models. In vitro studies with the K562 cell line demonstrated that compounds such as nipecotic acid, nicotinic acid, neosetofomon B, greensporone A and C, and isosuilin induce apoptosis, promote cell cycle arrest, and modulate crucial signaling pathways, including PI3K/AKT/mTOR and NF-κB at promising concentrations. The action of these metabolites involves the regulation of pro- and antiapoptotic proteins, caspase activation, and DNA damage, highlighting their ability to interfere with processes essential for the survival of leukemic cells. Alkaloids and terpenoids were the most promising classes observed. Although there have been important advances, it is still necessary to identify the mechanism of action of several compounds and their possible association with conventional anti-CML agents. FSM represents a valuable and still little-explored source for the development of new strategies for CML.