Anticancer Properties and Mechanism of Action of Oblongifolin C, Guttiferone K and Related Polyprenylated Acylphloroglucinols

Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants. Among them, the two related products oblongifolin C (Ob-C) and guttiferone K (Gt-K) isolated from Garcinia species (notably from edible fruits), have attracted attention due to their marked anticancer properties. The two compounds only differ by the nature of the C-6 side chain, prenyl (Gt-K) or geranyl (Ob-C) on the phloroglucinol core. Their origin, method of extraction and biological properties are presented here, with a focus on the targets and pathways implicated in their anticancer activities. Both compounds markedly reduce cancer cell proliferation in vitro, as well as tumor growth and metastasis in vivo. They are both potent inducer of tumor cell apoptosis, and regulation of autophagy flux is a hallmark of their mode of action. The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed. The specific role of the chaperone protein HSPA8, known to interact with Ob-C, is addressed. Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity. The review shed light on the mechanism of action of these compounds, to encourage their studies and potential development.