Ursolic acid, an antagonist for transforming growth factor (TGF)‐β1

Murakami, Shigeru; Takashima, Hajime; Sato-Watanabe, Mariko; Chonan, Sumi; Yamamoto, Kōji; Saitoh, Masako; Saito, Shiuji; Yoshimura, Hiromitsu; Sugawara, Koko; Yang, Jun‐Shan; Nannan, Gao; Zhang, Xinggao

doi:10.1016/j.febslet.2004.04.036

Cited by 37 publications

(29 citation statements)

References 30 publications

(30 reference statements)

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“…Some phenolic compounds and natural triterpenoids such as oleanolic, betulinic and ursolic acids have shown notable effects in suppressing tumourigenesis, as well as in inhibiting tumours (37)(38)(39)(40). Many nutritional and non-nutritional phytochemicals with diverse biological properties have shown promise in the prevention and/or treatment of prostate cancer (41).…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative effect of oleuropein in prostate cell lines

Vanella

2012

Int J Oncol

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Abstract. Currently, there is increasing interest in the in vivo protective effects of natural antioxidants found in dietary plants against oxidative damage caused by free radical species. Oxidative stress has been invoked as a causative agent in cancer and epidemiological data suggest that the consumption of fruits and vegetables may be associated with a lower incidence of cancer. The fruit of the Olea europaea L. and olive oil contain hundreds of phytochemicals and its extracts have recently been shown to exhibit antioxidant properties, due to the action of oleuropein. In view of these considerations, in this study, we investigated the effects of oleuropein on LNCaP and DU145 prostate cancer cell lines and on BPH-1 non-malignant cells. Oleuropein reduces cell viability and induces thiol group modifications, γ-glutamylcysteine synthetase, reactive oxygen species, pAkt and heme oxygenase-1. Exposing cell cultures to oleuropein induces an antioxidant effect on BPH-1 cells and a pro-oxidant effect on cancer cells. Our results confirm the beneficial properties of olive oil and oleuropein, suggesting its possible use as an adjuvant agent in the treatment of prostatitis, in order to prevent the transformation of hypertrophic to cancerous cells.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative effect of oleuropein in prostate cell lines

Vanella

2012

Int J Oncol

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“…New synthetic triterpenoids, at nanomolar concentrations, increase the expression of TGF-β-dependent genes, prolong TGF-β-induced Smad2 activation, markedly enhance the ability of Smad3 to activate Smad-binding elements in vitro, and have application in prevention or treatment of diseases like cancer and fibrosis in which there is aberrant function of TGF-β [159]. The triterpenoid ursolic acid functions as an antagonist of TGF-β and inhibits binding of TGF-β1 in mink lung epithelial cells [113]. Use of these triterpenoid agents in animal model systems will undoubtedly enhance our understanding of their potential for effectiveness.…”

Section: Tgf-β Antagonists For Inhibition Of Tumor Progressionmentioning

confidence: 99%

Transforming growth factor-β in cancer and metastasis

Jakowlew

2006

Cancer Metastasis Rev

480

386

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Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. The actions of TGF-beta are dependent on several factors including cell type, growth conditions, and the presence of other polypeptide growth factors. One of the biological effects of TGF-beta is the inhibition of proliferation of most normal epithelial cells using an autocrine mechanism of action, and this suggests a tumor suppressor role for TGF-beta. Loss of autocrine TGF-beta activity and/or responsiveness to exogenous TGF-beta appears to provide some epithelial cells with a growth advantage leading to malignant progression. This suggests a pro-oncogenic role for TGF-beta in addition to its tumor suppressor role. During the early phase of epithelial tumorigenesis, TGF-beta inhibits primary tumor development and growth by inducing cell cycle arrest and apoptosis. In late stages of tumor progression when tumor cells become resistant to growth inhibition by TGF-beta due to inactivation of the TGF-beta signaling pathway or aberrant regulation of the cell cycle, the role of TGF-beta becomes one of tumor promotion. Resistance to TGF-beta-mediated inhibition of proliferation is frequently observed in multiple human cancers, as are various alterations in the complex TGF-beta signaling and cell cycle pathways. TGF-beta can exert effects on tumor and stromal cells as well as alter the responsiveness of tumor cells to TGF-beta to stimulate invasion, angiogenesis, and metastasis, and to inhibit immune surveillance. Because of the dual role of TGF-beta as a tumor suppressor and pro-oncogenic factor, members of the TGF-beta signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis, as well as molecular targets for prevention and treatment of cancer and metastasis.

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“…Moreover, their beneficial effects have been analysed by extensive preclinical and epidemiological studies [1][2][3][4]. Some natural triterpenoids such as oleanolic, betulinic and ursolic acids have shown notable effects in suppressing tumourigenesis as well as inhibiting tumours [1,[5][6][7][8][9]. Also, a range of newly developed synthetic triterpenoids are more potent than the naturally occurring parent structure [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Also, a range of newly developed synthetic triterpenoids are more potent than the naturally occurring parent structure [10,11]. In addition, several of these compounds induce apoptosis in a wide variety of cancer cells, including breast carcinoma, melanoma, hepatoma, prostate carcinoma and acute myelogenous leukaemia [7]. To identify potential new anticancer compounds, several pharmaceutical companies are currently evaluating extracts from plants, among these new natural triterpenoids and their derivatives [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

(2α,3β)‐2,3‐Dihydroxyolean‐12‐en‐28‐oic acid, a new natural triterpene from Olea europea, induces caspase dependent apoptosis selectively in colon adenocarcinoma cells

et al. 2006

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Triterpenoids are known to induce apoptosis and to be anti-tumoural. Maslinic acid, a pentacyclic triterpene, is present in high concentrations in olive pomace. This study examines the response of HT29 and Caco-2 colon-cancer cell lines to maslinicacid treatment. At concentrations inhibiting cell growth by 50-80% (IC50HT29 = 61 ± 1 lM, IC80HT29 = 76 ± 1 lM and IC50Caco-2 = 85 ± 5 lM, IC80Caco-2 = 116 ± 5 lM), maslinic acid induced strong G0/G1 cell-cycle arrest and DNA fragmentation, and increased caspase-3 activity. However, maslinic acid did not alter the cell cycle or induce apoptosis in the nontumoural intestine cell lines IEC-6 and IEC-18. Moreover, maslinic acid induced cell differentiation in colon adenocarcinoma cells. These findings support a role for maslinic acid as a tumour suppressant and as a possible new therapeutic tool for aberrant cell proliferation in the colon. In this report, we demonstrate for the first time that, in tumoural cancer cells, maslinic acid exerts a significant anti-proliferation effect by inducing an apoptotic process characterized by caspase-3 activation by a p53-independent mechanism, which occurs via mitochondrial disturbances and cytochrome c release.

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Ursolic acid, an antagonist for transforming growth factor (TGF)‐β1

Cited by 37 publications

References 30 publications

Antiproliferative effect of oleuropein in prostate cell lines

Antiproliferative effect of oleuropein in prostate cell lines

Transforming growth factor-β in cancer and metastasis

(2α,3β)‐2,3‐Dihydroxyolean‐12‐en‐28‐oic acid, a new natural triterpene from Olea europea, induces caspase dependent apoptosis selectively in colon adenocarcinoma cells

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