Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy.

Abstract

Today cancer treatment is not only a question of eliminating cancer cells by induction of cell death. New therapeutic strategies also include targeting the tumour microenvironment, avoiding angiogenesis, modulating the immune response or the chronic inflammation that is often associated with cancer. Furthermore, the induction of redifferentiation of dedifferentiated cancer cells is an interesting aspect in developing new therapy strategies. Plants provide a broad spectrum of potential drug substances for cancer therapy with multifaceted effects and targets. Pentacyclic triterpenes are one group of promising secondary plant metabolites. This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action. Since Pisha et al. reported in 1995 that betulinic acid is a highly promising anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic acid and other triterpenes. The antitumour effects were subsequently confirmed in a series of cancer cell lines from other origins, for example breast, colon, lung and neuroblastoma. In addition, in the last decade many studies have shown further effects that justify the expectation that triterpenes are useful to treat cancer by several modes of action. Thus, triterpene acids are known mainly for their antiangiogenic effects as well as their differentiation inducing effects. In particular, lupane-type triterpenes, such as betulin, betulinic acid and lupeol, display anti-inflammatory activities which often accompany immune modulation. Triterpene acids as well as triterpene monoalcohols and diols also show an antioxidative potential. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high; although up to now no clinical trial has been published using these triterpenes in cancer therapy. They provide a multitarget potential for coping with new cancer strategies. Whether this is an effective approach for cancer treatment has to be proven. Because various triterpenes are an increasingly promising group of plant metabolites, the utilisation of different plants as their sources is of interest. Parts of plants, for example birch bark, rosemary leaves, apple peel and mistletoe shoots are rich in triterpenes and provide different triterpene compositions.