P52. The IKK inhibitors celastrol and parthenolide inhibit breast cancer cell proliferation and migration in vitro and osteolytic bone metastasis in vivo

Idris, Aymen I.; Libouban, Hélène; Nyangoga, Hervé; Landao-Bassonga, Euphemie; Chappard, Daniel; Ralston, Stuart H.

doi:10.1016/j.ctrv.2008.03.112

Cited by 3 publications

(9 citation statements)

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“…Osteoclast and osteoblast activity in the tumour microenvironment plays an essential role in the regulation of breast cancer cell behaviour in the skeleton [1][2][3][4]. The NF B signalling pathway regulates osteoclast and osteoblast differentiation in health and disease [16,34,47]. Previous studies have also implicated NFB in the initiation and progression of bone metastasis [33,34], and pharmacological inhibitors of NF B reduced breast cancer-induced osteolysis [33,34].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment regime used was chosen based on previous in vivo studies, which demonstrated that this agent has anti-resorptive and anti-metastatic effects [34]. Animals were euthanized 14 days post injection of 4T1-BT1 cells and bone architecture was assessed by micro-computed tomography (microCT, Brucker 1172 scanner, Brucker, Belgium) [41].…”

Section: Intra-tibial Injection In Micementioning

confidence: 99%

“…Over recent years, there has been increasing interest in the role of NF B in the regulation of breast cancer bone metastasis [33,34]. NF B in breast cancer cells enhances osteoclast formation and promotes bone metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…NF B in breast cancer cells enhances osteoclast formation and promotes bone metastasis. Recent work carried out in our laboratories has shown that pharmacologic inhibitors of NF B reduced osteolysis in a model of breast cancer osteolytic metastasis [33,34]. However, the role of NF Band its interaction with catenin -in the regulation of osteoblast and osteoclast changes associated with breast cancer-induced osteolysis has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…However, the role of NF Band its interaction with catenin -in the regulation of osteoblast and osteoclast changes associated with breast cancer-induced osteolysis has not been investigated. Using a pharmacological approach that utilizes data from experiments using bone cells, organ cultures and immuno-competent mice, we showed that the sesquiterpene lactone Parthenolide (PTN), a verified inhibitor of NFB [34][35][36][37], enhanced -catenin expression and activity in osteoblasts and osteoclasts in vitro, and protected against breast cancer-induced osteolysis ex vivo and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis

et al. 2017

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The NFκB signaling pathway is implicated in breast cancer and bone metastasis. However, the bone-autonomous contribution of NFκB to breast cancer-induced osteolysis is poorly understood. Here, we report that pretreatment of osteoblasts with the sesquiterpene lactone Parthenolide (PTN), a verified NFκB inhibitor, prior to exposure to conditioned medium from human and mouse breast cancer cell lines enhanced osteoblast differentiation and reduced osteoblast ability to stimulate osteoclastogenesis. PTN prevented breast cancer-induced osteoclast formation and reduced the ability of breast cancer cells to prolong osteoclast survival and to inhibit osteoclast apoptosis. In vivo, administration of PTN in immuno-competent mice reduced osteolytic bone loss and skeletal tumour growth following injection of the syngeneic 4T1-BT1 cells and reduced local osteolysis caused by conditioned medium from human and mouse osteotropic breast cancer cell lines. Mechanistic studies revealed that NFκB inhibition by PTN in osteoblasts and osteoclasts was accompanied by a significant increase in β-catenin activation and expression. Collectively, these results raise the possibility that combined targeting of NFκB and β-catenin signalling in the tumour microenvironment may be of value in the treatment of breast cancer related osteolysis.

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Section: Discussionmentioning

confidence: 99%

Section: Intra-tibial Injection In Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis

et al. 2017

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Triterpenoids with Cytotoxicity from Abelia engleriana

Xue

Zhao

et al. 2021

Chem Nat Compd

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Abelia engleriana (Graebn.) Rehder is a plant used as a food ingredient and belongs to the Abelia genus of the Caprifoliaceae family [1,2]. Jellies made from its leaves are famous snacks in Shaanxi Province, and the plant has extremely promising resources [3,4]. However, research on these resources are few and often focused on pectin. Moreover, the chemical constituents and bioactivity of A. engleriana have not been reported. In this study, the chemical constituents of A. engleriana were isolated and purified, and their cytotoxicity was evaluated. Seventeen triterpenoids were obtained and identified. They were abruslactone A (1) [5], eupatoric acid (2) [6], 3β-hydroxylup-9(11),12-dien-8-oic acid (3) [7], 3β-hydroxy-urs-12-en-29β-oic acid (4) [8], 3β-hydroxylup-12-en-28-oic acid (5) [9], methyl ursolate (6) [10], 27-hydroxy-α-amyranol (7) [11], lanostan-3β-ol (8) [12], oleanolic acid (9) [13], 3-hydroxy-11-ursene (10) [14], uvaol (11) [15], ursolic acid (12) [14], siaresinolic acid (13) [16], pomolic acid (14The GI 50 values of the isolated compounds against cell line HepG2, MCF-7, and A2058 are listed in Table 1. Only 3β-hydroxy-urs-12-en-29β-oic acid (4), 2α,3α-dihydroxy-urs-12-ene-28-oic acid ( 16), and 3 17) exhibited expressed cytotoxicity against cell line HepG2, MCF-7, and A2058.Pentacyclic triterpenes are the dominant triterpenoids in Caprifoliaceae plants. According to statistics, 34 new structures of triterpenoids were isolated from Caprifoliaceae plants from 1990 to 2018, of which 17 were dammarane types, eight were oleanidane types, four were lupine types, and five were fern alkane types [4]. Triterpenoids have antitumor activities with four main mechanisms of action. First, triterpenoids, such as ginsenoside [21,22], hawthorn acid [23], act directly on tumor cells and exert their antitumor effects by inhibiting proliferation and inducing apoptosis of tumor cells. Second, triterpenoids, particularly serpentine [24], act on tumor angiogenesis and inhibit the proliferation, migration, and tubule formation of vascular endothelial cell line ECV304 in vitro. Third, triterpenoids act on mitochondria; for example, ganoderma acid-t can induce the apoptosis of lung cancer cell line 95-d by increasing the expression level of p53 protein [25]. Fourth, triterpenoids act on related genes or proteins; ginsenoside Rg3 inhibits NF-κB and AP-1 transcription factors [26]. Our research showed that compounds 4, 16, and 17 exhibited expressed cytotoxicity against three cell lines, providing clues for further mechanism research.The plant was collected from the Qinling Mountain and was identified as Abelia engleriana (Graebn.) Rehder by Prof. Zenngjun Guo of Xi′an Jiaotong University. The powdered leaves of A. engleriana (10 kg) were extracted with 60% ethanol. The solvent was recovered and used in obtaining the total extract (2.19 kg), and the residues were suspended in water with an ultrasonic bath and successively partitioned with petroleum ether, chloroform, ethyl acetate, and butanol. Five subfractions were obtained.T...

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Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy

Nehybová¹,

Šmarda²,

Beneš

2014

ACAMC

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Natural products are often used in drug development due to their ability to form unique and diverse chemical structures. Coumestans are polycyclic aromatic plant secondary metabolites containing a coumestan moiety, which consists of a benzoxole fused to a chromen-2-one to form 1-Benzoxolo[3,2-c]chromen-6-one. These natural compounds are known for large number of biological activities. Many of their biological effects can be attributed to their action as phytoestrogens and polyphenols. In the last decade, anticancer effects of these compounds have been described in vitro but there is only limited number of studies based on models in vivo. More information concerning their in vivo bioavailability, stability, metabolism, toxicity, estrogenicity, cellular targets and drug interactions is therefore needed to proceed further to clinical studies. This review focuses on coumestans exhibiting anticancer properties and summarizes mechanisms of their toxicity to cancer cells. Moreover, the possible role of coumestans in cancer prevention is discussed.

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P52. The IKK inhibitors celastrol and parthenolide inhibit breast cancer cell proliferation and migration in vitro and osteolytic bone metastasis in vivo

Cited by 3 publications

References 0 publications

Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis

Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis

Triterpenoids with Cytotoxicity from Abelia engleriana

Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy

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