oleanane and Neoplasms

Natural pentacyclic triterpenoids (PTs) have been often reported to exhibit a wide range of biological activities. Among them, the anticancer and anti-inflammatory activities are the most studied. Over the last two decades, the number of publications reporting the anticancer effects of PTs has risen exponentially, reflecting the increasing interest in these natural products for the development of new antineoplastic drugs. Among of the most investigated PTs regarding their anticancer properties are oleanane-, ursane and friedelane-types, including oleanolic, glycyrrhetinic, ursolic and asiatic acids, and celastrol, among others. The extensive research in this field shows that the anticancer effects of PTs are mediated by several mechanisms, as they modulate a diverse range of molecular targets and signaling pathways, involved in cancer cell proliferation and survival. Considering the anticancer potential of this class of compounds, a number of semisynthetic derivatives has been synthetized aiming to improve their therapeutic activity and pharmacokinetic properties, and decrease their toxicity. Some of these new semisynthetic derivatives have shown improved anticancer activity in various cancer cell lines and animal models compared with the parent compound. Moreover, some of these compounds have been assessed in clinical trials, proving to be safe for human use. This review updates the most recent findings on the semisynthetic derivatives of oleanane-, ursane- and quinone methide friedelane-type PTs with anticancer activity. A brief introduction concerning the PTs and their anticancer activity is given, and the main semisynthetic modifications that have been performed between 2012 and early 2017 are reviewed and discussed.

Topics: Animals; Antineoplastic Agents; Chemistry Techniques, Synthetic; Humans; Indolequinones; Neoplasms; Oleanolic Acid; Structure-Activity Relationship; Triterpenes

Pentacyclic triterpenoids are a large class of natural isoprenoids that are widely biosynthesized in higher plants. These compounds are potent anticancer agents that exhibit antiproliferative, antiangiogenic, antiinflammatory and proapoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not yet been established. To date, a huge number of semisynthetic derivatives have been synthesized in different laboratories on the basis of triterpenoid scaffolds, and many have been assayed for their biological activities. The present review focuses on natural triterpenoids of the oleanane-, ursane- and lupane-types and their semisynthetic derivatives. Here, we summarize the diverse cellular and molecular targets of these compounds and the signal pathways involved in the performance of their antitumour actions. Among the most relevant mechanisms involved are cell cycle arrest, apoptosis and autophagy triggered by the effect of triterpenoids on TGF-β and HER cell surface receptors and the downstream PI3KAkt- mTOR and IKK/NF-kB signaling axis, STAT3 pathway and MAPK cascades.

Topics: Antineoplastic Agents; Apoptosis; Humans; Neoplasms; NF-kappa B; Oleanolic Acid; Signal Transduction; Transforming Growth Factor beta; Triterpenes

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: Antineoplastic Agents, Phytogenic; Humans; Neoplasms; Oleanolic Acid; Pentacyclic Triterpenes; Phytotherapy; Plant Extracts; Triterpenes

I have an opportunity to have co-operative studies with Chinese group of Kunming Institute of Botany. Since then, I have investigated the chemical constituents of a number of Chinese plants of Araliaceae, Umbelliferae, Labiatae, Cucurbitaceae and other families. This review describes the structural elucidation of the cucurbitane, oleanane and dammarane glycosides, and their biological activities under the joint studies on cucurbitaceous plants, Bolbostemma, Hemsleya, Siraitia and Neoalsomitra species. New oleanane glycosides having novel cyclic structure were isolated from Bolbostemma paniculatum. The potent solubilizing effect of these compounds was investigated. A number of cucurbitane glycosides were isolated from Hemsleya carnosiflora, H. panacis-scandens, Siraitia grosvenorii and S. siamensis. Some of these glycosides taste sweet, bitter or tasteless. The structure-taste relationships of the glycosides of a 3-alpha-hydroxy-cucurbit-5-ene-type triterpene have been discussed. Anti-tumor-promotion effects as well as the ecdysteroid agonist and antagonist activities of these cucurbitane glycosides were investigated. New dammarane glycosides were isolated from Neoalsomitra integrifoliola.

Topics: Animals; Cell Division; Cucurbitaceae; Dammaranes; Dose-Response Relationship, Drug; Ecdysteroids; Glycosides; Humans; Micelles; Molecular Conformation; Neoplasms; Neovascularization, Physiologic; Oleanolic Acid; Solubility; Structure-Activity Relationship; Taste; Triterpenes; Tumor Cells, Cultured

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antineoplastic Agents; Dose-Response Relationship, Drug; Humans; Mice; Neoplasms; Oleanolic Acid; Retinoid X Receptors

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Topics: Antineoplastic Agents, Phytogenic; Ardisia; Epoxy Compounds; Humans; Neoplasms; Oleanolic Acid; Plant Extracts; Plant Roots; Saponins; Triterpenes; Tumor Cells, Cultured

Reaction of 3-O-acetyl-oleanolic acid (3) with formic acid/hydrogen peroxide at 100 °C for several hours provides an extraordinary but simple pathway to a taraxeran-28,14 β -olide type triterpenoid while the same reaction at 0 °C occurred without re-arrangement of the carbon skeleton, and an oleanane-28,13 β -olide was obtained instead. The products from these reactions were subjected to a cytotoxicity screening employing several human tumor cell lines showing the latter compound not cytotoxic while the former was cytotoxic especially for MCF-7 (breast adenocarcinoma), and FaDu (hypopharyngeal carcinoma) cells. The highest cytotoxicity, however, was observed for 3 β, 12α, 13 β -trihydroxy-oleanan-28-oic acid (6) holding with EC

Topics: Antineoplastic Agents; Cell Proliferation; Humans; Molecular Structure; Neoplasms; Oleanolic Acid; Triterpenes; Tumor Cells, Cultured

Two new oleanane-type triterpenes named ivorengenin A (=3-oxo-2α,19α,24-trihydroxyolean-12-en-28-oic acid; 1) and ivorengenin B (=4-oxo-19α-hydroxy-3,24-dinor-2,4-secoolean-12-ene-2,28-dioic acid; 2), together with five known compounds, arjungenin, arjunic acid, betulinic acid, sericic acid, and oleanolic acid, were isolated from the barks of Terminalia ivorensis A. Chev. (Combretaceae). Their structures were established on the basis of 1D- and 2D-NMR data, and mass spectrometry. A biogenetic pathway to the formation of these compounds from sericic acid, isolated as the major compound from this plant, was proposed. The antioxidant activities of different compounds were investigated by means of the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, and IC(50) values were calculated and compared with Trolox activity. Antiproliferative activities of the isolated compounds were also evaluated against MDA-MB-231, PC3, HCT116, and T98G human cancer cell lines, against which the compounds showed significant cytotoxic activities.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Neoplasms; Oleanolic Acid; Terminalia; Triterpenes