Anticancer Activity of 2α, 3α, 19β, 23β-Tetrahydroxyurs-12-en-28-oic Acid (THA), a Novel Triterpenoid Isolated from Sinojackia sarcocarpa

BACKGROUND: Natural products represent an important source for agents of cancer prevention and cancer treatment. More than 60% of conventional anticancer drugs are derived from natural sources, particularly from plant-derived materials. In this study, 2α, 3α, 19β, 23β-tetrahydroxyurs-12-en-28-oic acid (THA), a novel triterpenoid from the leaves of Sinojackia sarcocarpa, was isolated, and its anticancer activity was investigated both in vitro and in vivo. PRINCIPAL FINDINGS: THA possessed potent tumor selected toxicity in vitro. It exhibited significantly higher cytotoxicity to the cancer cell lines A2780 and HepG2 than to IOSE144 and QSG7701, two noncancerous cell lines derived from ovary epithelium and liver, respectively. Moreover, THA showed a dose-dependent inhibitory effect on A2780 ovary tumor growth in vivo in nude mice. THA induced a dose-dependent apoptosis and G2/M cell cycle arrest in A2780 and HepG2 cells. The THA-induced cell cycle arrest was accompanied by a downregulation of Cdc2. The apoptosis induced by THA was evident by induction of DNA fragmentation, release of cytoplasmic Cytochrome c from mitochondria, activation of caspases, downregulation of Bcl-2 and upregulation of Bax. CONCLUSION: The primary data indicated that THA exhibit a high toxicity toward two cancer cells than their respective non-cancerous counterparts and has a significant anticancer activity both in vitro and in vivo. Thus, THA and/or its derivatives may have great potential in the prevention and treatment of human ovary tumors and other malignancies

A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo

Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML