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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.
Topics: Pentacyclic Triterpenes (58%), Triterpene (57%), Oleanane (57%), Betulin (54%), Betulinic acid (53%)
Citations
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Journal ArticleDOI
TL;DR: The most comprehensive picture over SFE of vegetable matrices is provided in this review, highlighting pertinent aspects and opportunities that may further consolidate the convincing route of this technology for the next years.
Abstract: Along more than a decade, R&D on supercritical fluid extraction (SFE) of vegetable matrices has been increasingly reported in the literature. Aiming at portraying the current state of this field and its evolution in terms of raw materials, products, modes of operation, optimization, modeling techniques, and closeness to industrial application, a large compilation of almost 600 essays from 2000 to 2013 has been deeply analyzed in order to unveil those indicators and their trends. Furthermore, strengths and weaknesses are identified, and some remarks that may drive upcoming research are provided. Globally, more than 300 species are reported in the literature, with prevalence of the extraction of seeds (28% of works) and leaves (17%). The main families of extracted compounds, cosolvents and operating conditions adopted are critically examined, being possible to conclude that researchers investigate many times working regions far from the optimum due to practical limitations or absence of experimental optimization. Current phenomenological, statistical and semi-empirical approaches are reviewed, along with scale-up studies, and economic analysis. In the whole, the most comprehensive picture over SFE of vegetable matrices is provided in this review, highlighting pertinent aspects and opportunities that may further consolidate the convincing route of this technology for the next years.

324 citations


Journal ArticleDOI
Roslin J. Thoppil1, Anupam BishayeeInstitutions (1)
TL;DR: This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors.
Abstract: Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.

252 citations


Journal ArticleDOI
TL;DR: The industrial uses and potential of saponins are discussed with respect to structure and activity, highlighting the undoubted value of these molecules as therapeutics.
Abstract: Saponins are widely distributed plant natural products with vast structural and functional diversity. They are typically composed of a hydrophobic aglycone, which is extensively decorated with functional groups prior to the addition of hydrophilic sugar moieties, to result in surface-active amphipathic compounds. The saponins are broadly classified as triterpenoids, steroids or steroidal glycoalkaloids, based on the aglycone structure from which they are derived. The saponins and their biosynthetic intermediates display a variety of biological activities of interest to the pharmaceutical, cosmetic and food sectors. Although their relevance in industrial applications has long been recognized, their role in plants is underexplored. Recent research on modulating native pathway flux in saponin biosynthesis has demonstrated the roles of saponins and their biosynthetic intermediates in plant growth and development. Here, we review the literature on the effects of these molecules on plant physiology, which collectively implicate them in plant primary processes. The industrial uses and potential of saponins are discussed with respect to structure and activity, highlighting the undoubted value of these molecules as therapeutics.

246 citations


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

  • ...…by natural and semi-synthetic triterpenoids, alongside the triterpenoid and steroidal saponins and steroidal glycoalkaloids (Kannaiyan et al., 2011; Laszczyk, 2009; Lee et al., 2011; Liby & Sporn, 2012; Pollier & Goossens, 2012; Raju & Mehta, 2009; Shanmugam et al., 2013; Wu et al., 2007; Yadav et…...

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Journal ArticleDOI
TL;DR: In vitro and in vivo effects of these agents and related molecular mechanisms are presented and potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are identified.
Abstract: Breast cancer remains a major cause of death in the United States as well as the rest of the world. In view of the limited treatment options for patients with advanced breast cancer, preventive and novel therapeutic approaches play an important role in combating this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, posses various pharmacological properties. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells as well as anticancer efficacy in preclinical animal models. Numerous triterpenoids have been synthesized by structural modification of natural compounds. Some of these analogs are considered to be the most potent antiinflammatory and anticarcinogenic triterpenoids known. This review examines the potential role of natural triterpenoids and their derivatives in the chemoprevention and treatment of mammary tumors. Both in vitro and in vivo effects of these agents and related molecular mechanisms are presented. Potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are also identified.

231 citations


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

  • ...They predominantly are found in various plants including seaweeds as well as in wax-like coatings of various fruits and medicinal herbs, including apples, cranberries, figs, olives, mistletoe, lavender, oregano, rosemary and thyme (21, 26, 28-30)....

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  • ...An increasing number of triterpenoids have been reported to exhibit cytotoxicity against a variety of cancer cells without manifesting any toxicity in normal cells (24, 26, 27)....

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  • ...The use of triterpenoids and related compounds for either chemoprevention or therapy of mammary carcinoma has not been extensively discussed previously although several excellent articles provide an overview of the antitumor potential of these agents against various cancers (24-27)....

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  • ...They also demonstrate antitumor efficacy in preclinical animal models of cancer (26, 27)....

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Journal ArticleDOI
TL;DR: This review not only summarizes the diverse molecular targets of ursolic acid, but also provides an insight into the various preclinical and clinical studies that have been performed in the last decade with this promising triterpenoid.
Abstract: Discovery of bioactive molecules and elucidation of their molecular mechanisms open up an enormous opportunity for the development of improved therapy for different inflammatory diseases, including cancer. Triterpenoids isolated several decades ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments and some have already entered Phase I clinical trials. One such important and highly investigated pentacyclic triterpenoid, ursolic acid has attracted great attention of late for its potential as a chemopreventive and chemotherapeutic agent in various types of cancer. Ursolic acid has been shown to target multiple proinflammatory transcription factors, cell cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of ursolic acid by inhibiting the initiation, promotion and metastasis of cancer. This review not only summarizes the diverse molecular targets of ursolic acid, but also provides an insight into the various preclinical and clinical studies that have been performed in the last decade with this promising triterpenoid.

225 citations


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

  • ...Recent evidences have supported the beneficial effects of ursolic acid in a variety of human diseases, including various types of inflammation-driven cancers [11]....

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Journal ArticleDOI
Jie Liu1Institutions (1)
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.
Abstract: Oleanolic acid and ursolic acid are triterpenoid compounds that exist widely in food, medicinal herbs and other plants. This review summarizes the pharmacological studies on these two triterpenoids. Both oleanolic acid and ursolic acid are effective in protecting against chemically induced liver injury in laboratory animals. Oleanolic acid has been marketed in China as an oral drug for human liver disorders. The mechanism of hepatoprotection by these two compounds may involve the inhibition of toxicant activation and the enhancement of the body defense systems. Oleanolic acid and ursolic acid have also been long-recognized to have antiinflammatory and antihyperlipidemic properties in laboratory animals, and more research is warranted to develop a therapy for patients. Recently, both compounds have been noted for their antitumor-promotion effects, which are stimulating additional research in this field. Oleanolic acid and ursolic acid are relatively non-toxic, and have been used in cosmetics and health products. The possible mechanisms for the pharmacological effects and the prospects for these two compounds are discussed.

1,267 citations


Journal ArticleDOI
E. Pisha1, Heebyung Chai1, Ik-Soo Lee1, T E Chagwedera2  +7 moreInstitutions (4)
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.

783 citations


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No. of citations received by the Paper in previous years
YearCitations
202136
202028
201936
201836
201732
201638