New targets for the antitumor activity of gambogic acid in hematologic malignancies

Abstract

Gambogic acid (GA) is the main active ingredient of gamboge, a brownish to orange dry resin secreted from Garcinia hanburyi, a plant that is widely distributed in nature. Recent in vitro and in vivo studies have demonstrated that GA exerts potent antitumor effects against solid tumors of various derivations, and its antitumor mechanisms have been thoroughly investigated. On the other hand, normal cells remain relatively resistant to GA, indicating a therapeutic window. GA is currently in clinical trials in China. Over the last decade, our laboratory demonstrates that GA exhibits potent anticancer activities against hematological malignancies. This review focuses on the new mechanisms through which GA inhibits proliferation and induces apoptosis in malignant hematological cells. These include the regulation of expression and intracellular positioning of nucleoporin and nucleophosmin; downregulation of steroid receptor coactivator-3 (SRC-3) and its downstream proteins; upregulation of death inducer-obliterator (DIO-1); downregulation of HERG potassium channel; as well as induction of reactive oxygen species (ROS) accumulation.

Caged Garcinia Xanthones, a Novel Chemical Scaffold with Potent Antimalarial Activity

“…This motif is further decorated via A-ring substitutions and peripheral oxidations to produce a variety of natural products with a broad range of bioactivities (11). Gambogic acid (GBA), the archetype of this family, potently inhibits cancer cell proliferation in solid tumors (13)(14)(15)(16)(17) and hematological malignancies (18) and has entered clinical trials in China for patients with non-small-cell lung, colon, and renal cancers (19). In addition, the potent cytotoxicity of several CGXs at low micromolar concentrations has been well documented (20)(21)(22)(23).…”

Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non-Hodgkin lymphoma and an inducer of histone H3 deacetylation

“…Gambogic acid is a brownish to orange dry resin secreted from Garcinia hanburyi, which mainly grows in South China, Cambodia, Vietnam, and Thailand (Yang and Chen, 2013).…”

“…In recent decades, both in vitro and in vivo evidence revealed the potent anti-tumor efficacies of GA, not only in solid tumors Ishaq et al, 2014;Zhao et al, 2008;Park et al, 2015), but also in hematological malignancies (Gupta et al, 2010;Prasad et al, 2011;Yang and Chen, 2013). However, the anti-tumor efficacies of GA in B-cell NHL and the underlying mechanism have not been fully uncovered.…”

G226, a new epipolythiodioxopiperazine derivative, triggers DNA damage and apoptosis in human cancer cells in vitro via ROS generation

“…Although ROS are maintained at low levels via various enzyme systems participating in the in vivo redox homeostasis, many factors, including endogenous biological or exogenous environmental factors, can induce an imbalance between the pro-oxidants and antioxidants or alter enzyme activity, as observed with npg chemical exposure, drugs, pollution, or radiation [4] . ROS have also been implicated in the antitumor effects of some anticancer drugs [9,10] . A number of anticancer drugs produce ROS at various cellular sites in vivo.…”