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Journal ArticleDOI

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

01 Dec 2009-Planta Medica (© Georg Thieme Verlag KG Stuttgart · New York)-Vol. 75, Iss: 15, pp 1549-1560
TL;DR: This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action and utilisation of different plants as their sources is of interest.
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.

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Citations
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Journal ArticleDOI
TL;DR: This review compiles the most relevant lanostanoids studied from 2000 to 2011, principally those isolated from Ganoderma lucidum and other related fungi, which have great potential as anticancer agents because of their cytotoxic or apoptotic effects.
Abstract: Lanostanes are a group of tetracyclic triterpenoids derived from lanosterol. They have relevant biological and pharmacological properties, such as their cytotoxic effects via induction of apoptosis. This review compiles the most relevant lanostanoids studied from 2000 to 2011, principally those isolated from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata, which have great potential as anticancer agents because of their cytotoxic or apoptotic effects. The compounds were selected on the basis of their proapoptotic mechanisms, through their ability to modify transcriptional activities via nuclear factors or genes and the activation or inhibition of pro- or antiapoptotic proteins; studies based only on their cytotoxicity were excluded from this review in the absence of complementary studies on their mechanisms of action. A total of 81 compounds from Ganoderma lucidum and other species from this genus are included, as well as 96 compounds isolated from other fungi, principally Poria cocos. Some of these compounds were found to arrest the cell cycle in the G1 phase, increase levels of p53 and Bax, or inhibit the phosphorylation of Erk1/2 or the activation of NF-κB and AP-1. Other lanostanes have inhibitory effects on the growth of androgen prostate carcinoma through increasing the expression of p21, which activates the tumor suppressor protein p53, while other compounds have been shown to selectively inhibit topo II activity without affecting topo I. General considerations concerning the chemical structure-biological activities of these compounds are also discussed.

124 citations

Journal ArticleDOI
TL;DR: The aim of this review is to comprehensively summarise the potential of betulin and betulinic acid, both in vitro and in vivo, including previous studies of anti-cancer activity of the compounds, with listed cancer cell types susceptible to therapy.
Abstract: Betulin, a pentacyclic triterpene and a plant pentacyclic triterpene metabolite, can be found in large quantities in the outer bark of the birches (Betula, Betulaceae). Betulinic acid, obtained by betulin oxidation, is also abundantly present in nature. Both compounds show a wide spectrum of biological and pharmacological properties, such as anti-HIV, anti-inflammatory, and, considered the most important, anti-cancer. Although the specific mechanism of action of betulin against malignant cells is still a subject of detailed research, the activity of betulin acid has been linked to the induction of the intrinsic pathway of apoptosis. As this process occurs with the sparing of non-cancer cells, and the induction of apoptosis can occur under conditions in which standard therapies fail, both substances seem as promising experimental anti-cancer drugs. The aim of this review is to comprehensively summarise the potential of betulin and betulinic acid, both in vitro and in vivo. The discovery, structure, organic synthesis and derivatives forming were shortly described. Also, the potential molecular mechanisms of action and numerous medical applications of betulin and betulinic acid were presented, including previous studies of anti-cancer activity of the compounds, with listed cancer cell types susceptible to therapy.

123 citations


Cites methods from "Pentacyclic triterpenes of the lupa..."

  • ...By successfully combining the expression of the C28 oxidase from C. roseus and lupeol synthase from A. thaliana, BA was obtained in Saccharomyces cerevisiae from endogenous yeast 2,3-oxidosqualene (Huang et al. 2012; Li and Zhang 2014, 2015)....

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Journal ArticleDOI
TL;DR: This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore of Spastic Paraplegia 7, a mitochondrial AAA-type membrane protease which forms a 6-stave barrel.

121 citations

Journal ArticleDOI
TL;DR: Recent advances in research into anticancer activity of BetA are discussed, including relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug.
Abstract: An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

117 citations

Journal ArticleDOI
TL;DR: This review highlights the potential of natural and semisynthetic ursane-type triterpenoids as candidates for the design of multi-target bioactive compounds, with focus on their anticancer effects.

115 citations

References
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TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

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24 Jul 2008-Nature
TL;DR: The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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Journal ArticleDOI
Jie Liu1
TL;DR: Both oleanolic acid and ursolic acid are effective in protecting against chemically induced liver injury in laboratory animals and have been noted for their antitumor-promotion effects, which are stimulating additional research in this field.

1,345 citations

Journal ArticleDOI
TL;DR: As a result of bioassay–guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma–specific cytotoxic agent and antitumour activity was mediated by the induction of apoptosis.
Abstract: As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

829 citations