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

Abstract

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.

Constituents of the Stem Bark of Symphonia globulifera Linn. f. with Antileishmanial and Antibacterial Activities

“…The 13 C NMR spectrum ( Table 1 ) of 1 revealed 38 carbon signals, which were sorted by DEPT and HMBC experiments into eight methyls, eight methylenes, seven methines [including three aromatic carbons at ẟ C 116.6 (C-12), 114.2 (C-15), and 123.9 (C-16)], and fifteen quaternary carbons. The carbon spectrum also displayed typical signals of a bicyclo[3.3.1]nonane ring system that included one ketone [ẟ C 208.8 (C-9)], an enolized 1,3-diketone [ẟ C 196.5 (C-1), 193.9 (C-10), 116.1 (C-2), and 191.9 (C-3)], three quaternary carbons [ẟ C 70.3 (C-4), 51.8 (C-5), and 57.8 (C-8)], one methine at ẟ C 39.7 (C-6), and a methylene at ẟ C 43.3 (C-7) [ 37 ]. All these spectral data are close to those of guttiferone A, a polyisoprenylated benzophenone [ 38 ].…”

“…The duplication of all these data in association with the mass data confirmed that 2/3 was a mixture of two polyisoprenylated benzophenone derivatives. The 13 C NMR spectrum of 2/3 displayed characteristic signals for a bicyclo[3.3.1]nonane ring as pairs of carbons at ẟ C 170.3/170.5 (C-1), 125.6/125.9 (C-2), 193.3/193.6 (C-3), 68.9/69.0 (C-4), 48.3/48.4 (C-5), 2×39.4 (C-6), 38.1/38.3 (C-7), 51.2/51.5 (C-8), and 206.2/206.3 (C-9) [ 37 , 39 ].…”

Rhodomyrtus tomentosa as a new anticancer molecular strategy in breast histology via Her2, IL33, EGFR, and MUC1

“…In a malignant immune system, IL-33 can promote or inhibit tumor growth ( Gao et al, 2015 ). The latest study has revealed that IL-33 can, directly and indirectly, promote antitumor activity by stimulating immunological effector cells such as TNK, CD8 + , and white blood cell members ( Bailly and Vergoten, 2021 ). Tissue-specific environmental variables may control the equilibrium of IL-33-induced immunological reactions, while the relevance of IL-33 in cancer immunity remains debatable ( Zhang et al, 2022 ).…”

“…Tissue-specific environmental variables may control the equilibrium of IL-33-induced immunological reactions, while the relevance of IL-33 in cancer immunity remains debatable ( Zhang et al, 2022 ). During viral infection, IL-33 expression increases, and oxidative stress in breast tissue is involved in IL-33 expression in epithelial cells via the MAPK signaling pathway ( Bailly and Vergoten, 2021 ). Acylploroglucinols can be found in haramonting.…”

Liposome-Encapsulated Bioactive Guttiferone E Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated MH-S Macrophages and Cytotoxicity against Human Cancer Cells

“…GE has been reported to exert a wide range of biological activities including anti-inflammatory and cytotoxic effects against cancer cells [8]. Its anti-inflammatory mechanism includes the targeting of the TLR/IRAK-1 pathway and inhibition of the downstream NF-κB and Akt/mTOR signaling pathways and the inhibition of the activity of lipoxygenase enzymes and the production of nitric oxide in LPS-stimulated RAW 264.7 macrophages [9][10][11]. GE has been reported to display cytotoxic activity in HCT 116, HT 29, and SW-480 human colon cancer cell lines, in the KB oral carcinoma cell line, and in various sensitive and drugresistant phenotype cancer cells including breast adenocarcinoma MDA-MB-231-BCRP cells [12][13][14].…”