Highlights of Pentacyclic Triterpenoids in the Cancer Settings

Salvador, Jorge A. R.; Leal, Ana S.; Alho, Daniela P.S.; Gonçalves, Bruno M. F.; Valdeira, Ana S.; Mendes, Vanessa I.S.; Jing, Yongkui

doi:10.1016/b978-0-444-63294-4.00002-4

Cited by 52 publications

(32 citation statements)

References 247 publications

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“…1) [4–7]. Based on the extensive summaries of these compounds and other active triterpenoids [4–7], it is evident that many structurally diverse triterpenoids and their synthetic analogs give overlapping activities; however, direct comparisons of the effects of different triterpenoids are limited and incomplete since most studies have examined diverse responses in different cell lines. Similarities and differences in the effects of various triterpenoids is also complicated by cell context-dependent differences.…”

Section: The Anticancer Activities Of Triterpenoidsmentioning

confidence: 99%

“…For example, almost all pentacyclic triterpenoids induce apoptosis and inhibit growth of cancer cells derived from solid and non-solid tumors. The pentacyclic triterpenoid compounds also affect cell cycle progression, angiogenic, metastatic and anti-inflammatory responses; however, these responses have been determined only in a limited number of cell lines [4–7]. Moreover, most reports have focused only on one or two pathways and with the exception of some receptor studies (see next section), the specific sub-cellular receptors or acceptors that are bound or activated by pentacyclic triterpenoids have not been extensively investigated or identified.…”

Section: The Anticancer Activities Of Triterpenoidsmentioning

confidence: 99%

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Unifying Mechanisms of Action of the Anticancer Activities of Triterpenoids and Synthetic Analogs

Safe¹,

Prather²,

Brents³

et al. 2012

ACAMC

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Triterpenoids such as betulinic acid (BA) and synthetic analogs of oleanolic acid [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)] and glycyrrhetinic acid [2-cyano-3,11-dioxo-18β-oleana-1,12-dien-30-oc acid (CDODA)] are potent anticancer agents that exhibit antiproliferative, antiangiogenic, anti-inflammatory and pro-apoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not been reported. Studies in this laboratory have now demonstrated that several triterpenoids including BA and some derivatives, celastrol, methyl ursolatee, β-boswellic acid derivatives, and the synthetic analogs CDDO, CDODA and their esters decreased expression of specificity protein (Sp) transcription factors and several pro-oncogenic Sp-regulated genes in multiple cancer cell lines. The mechanisms of this response are both compound- and cell context-dependent and include activation of both proteasome-dependent and -independent pathways. Triterpenoid-mediated induction of reactive oxygen species (ROS) has now been characterized as an important proteasome-independent pathway for downregulation of Sp transcription factors. ROS decreases expression of microRNA-27a (miR-27a) and miR-20a/miR-17-5p and this results in the induction of the transcriptional “Sp-repressors” ZBTB10 and ZBTB4, respectively, which in turn downregulate Sp and Sp-regulated genes. Triterpenoids also activate or deactive nuclear receptors and G-protein coupled receptors, and these pathways contribute to their antitumorigenic activity and may also play a role in targeting Sp1, Sp3 and Sp4 which are highly overexpressed in multiple cancers and appear to be important for maintaining the cancer phenotype.

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Section: The Anticancer Activities Of Triterpenoidsmentioning

confidence: 99%

Section: The Anticancer Activities Of Triterpenoidsmentioning

confidence: 99%

Unifying Mechanisms of Action of the Anticancer Activities of Triterpenoids and Synthetic Analogs

Safe¹,

Prather²,

Brents³

et al. 2012

ACAMC

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show abstract

“…This pharmacological significance has made triterpenoids one of the most studied families of natural products in recent decades (Hill and Connolly, 2015;Han and Peng, 2014;Nazaruk and Borzym-Kluczyk, 2014;Salvador et al, 2014;Parmar et al, 2013;Petronelli et al, 2009).…”

Section: Introductionmentioning

confidence: 97%

Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

et al. 2015

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“…As anti-tumor effects are the most classical activities of oleanolic acid and its derivatives [1, 27–29], these conjugates have been evaluated by MTT assay [30, 31] against 5 adherent tumor cell lines (Hep-G2, A549, BGC-823, MCF-7 and PC-3) with 1 as the positive control. 5-Fluorouracil (5-FU), a medication used in the clinical treatment of cancer, is also a pyrimidine analog and was used as a positive control in this study.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of acyl oleanolic acid-uracil conjugates and their anti-tumor activity

Wei-bin

Huang

et al. 2016

Chemistry Central Journal

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BackgroundOleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies.ResultsFive acyl oleanolic acid-uracil conjugates were synthesized. Most of the IC50 values of these conjugates were lower than 10.0 μM, and some of them were even under 0.1 μM. Cytotoxicity selectivity detection revealed that conjugate 4c exhibited low cytotoxicity towards the normal human liver cell line HL-7702. Further studies revealed that 4c clearly possessed apoptosis inducing effects, could arrest the Hep-G2 cell line in the G1 phase, induce late-stage apoptosis, and activate effector caspase-3/9 to trigger apoptosis.ConclusionsConjugates of five different acyl OA derivatives with uracil were synthesized and identified as possessing high selectivity toward tumor cell lines. These conjugates could induce apoptosis in Hep-G2 cells by triggering caspase-3/9 activity.Graphical abstractFive acyl oleanolic aicd-uracil conjugates were synthesized. These conjugates exhibited selective cytotoxicity toward tumor cells achieved via inducing apoptosis by activation of caspase-3/9. Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0217-5) contains supplementary material, which is available to authorized users.

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Highlights of Pentacyclic Triterpenoids in the Cancer Settings

Cited by 52 publications

References 247 publications

Unifying Mechanisms of Action of the Anticancer Activities of Triterpenoids and Synthetic Analogs

Unifying Mechanisms of Action of the Anticancer Activities of Triterpenoids and Synthetic Analogs

Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

Synthesis of acyl oleanolic acid-uracil conjugates and their anti-tumor activity

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