Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility

Bijman, Marcel N.A.; Berkel, Maria P.A. van; Amerongen, Geerten P. van Nieuw; Boven, Epie

doi:10.1016/j.bcp.2008.06.014

Cited by 23 publications

(24 citation statements)

References 29 publications

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“…These results suggest that docetaxel inhibits local invasion of head and neck cancer cells. Although the effect of docetaxel on cell migration and invasiveness of ovary cancer cells, (28) umbilical vein endothelial cells, (29) and glioma cells (30) has been described, its effect on head and neck cancer cells has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Docetaxel suppresses invasiveness of head and neck cancer cells in vitro

et al. 2010

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The combination of docetaxel, cisplatin, and fluorouracil significantly enhances the survival of head and neck cancer patients compared to cisplatin and fluorouracil. We hypothesized that docetaxel may affect invasiveness of the head and neck cancer cells in addition to its tumor-killing effect. Two different head and neck cancer cell lines (HEp-2 and Ca9-22) were treated with docetaxel at IC 10 and IC 50 concentrations. Cell migration and invasive growth was evaluated by wound healing assay and three-dimensional (3D) culture of multicellular tumor spheroids, respectively. Expression levels of possible downstream effectors for cell migration ⁄ invasiveness were measured by immunoblotting in conditions with or without docetaxel. Docetaxel, but not cisplatin, suppressed filopodia formation compared with no treatment (control) condition. Consistent with this, docetaxel suppressed two-dimensional (2D) cell migration and 3D cell invasion compared with control or cisplatin. Only docetaxel treated cells exhibited thick tubulin bundle and had lower activity of Cdc42, a member of the Rho family of small GTPases. In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity. (Cancer Sci 2010; 101: 1382-1386 S quamous cell carcinoma (SCC) of the head and neck accounts for 5% of cancers in adults worldwide.(1) The disease is potentially curable at an early stage, but most patients present with locally advanced disease. Only 30-50% of patients with locally advanced disease live for 3 years after surgery and radiation therapy. Locoregional recurrences or distant metastases develop in 40-60% of them.(2-5) Moreover, radical resection of the tumor, which results in loss of the larynx, severely compromises quality of life in such patients. In order to increase the survival rate and preserve voice and swallowing function over surgery and radiation alone, various supplementary chemotherapy regimens have been developed. (6)(7)(8) Recently it was reported that the combination of docetaxel, cisplatin, and fluorouracil (TPF) followed by chemoradiotherapy significantly enhances survival of head and neck cancer patients compared to cisplatin and fluorouracil (PF) followed by chemoradiotherapy.(9) Estimates of overall survival at 3 years were 62% in the TPF and 48% in the PF groups. It was also reported that incidence of distant metastasis is lower in the TPF (5% vs 9%), although it does not reach statistical significance. We therefore hypothesized that docetaxel may affect migration and invasiveness of the head and neck cancer cells. The mechanism of antitumor effect of the taxanes, such as docetaxel is thought to be the stabilization of microtubules during mitosis, which leads to blockade of cell division and eventually cell death. However, the effect of docetaxel on cell invasiveness has not been evaluated in head and neck cancers. We demonstrate here that docetaxel inhibited migration of head and neck cancer cells in vitro, ...

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Section: Discussionmentioning

confidence: 99%

Docetaxel suppresses invasiveness of head and neck cancer cells in vitro

et al. 2010

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“…The induction of apoptosis through the detachment from ECM has been know as "anoikis." 13) Effects of GA on Cytoskeletal Proteins in r/m HM-SFME-1 Cells The results of the morphologic and anoikislike effects by GA in the present study prompted us to analyze the actin and microtubule cytoskeletons, since together they provide the cell shape and maintain the cellular structure 14) and disruption of structural elements might trigger anoikis. 15) After GA treatment at 10 mM for 8 and 24 h, Factin and bIII-tubulin were analyzed by immunofluorescence staining and confocal laser-scanning microscopic observation.…”

Section: Resultsmentioning

confidence: 88%

“…These results indicate that GA causes disturbances in these cytoskeletal proteins, which could lead to loss of functionality for cell structure and result in the anoikis-like cell death. It has been reported that interference with actin or microtubule functions associated with the integrity of the cytoskeleton, even without affecting the amount of the cytoskeletal proteins, could be utilized as a strategy for developing novel antitumor treatments, 14) which suggests that qualitative changes in the cytoskeleton are of very importance. In fact, our results are in agreement with the previous report which suggested that disruption of cytoskeletal proteins was associated with the induction of anoikis in cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Glycyrrhetinic Acid Induces Anoikis-Like Death and Cytoskeletal Disruption in the Central Nervous System Tumorigenic Cells

Yamaguchi

Kidachi

Kamiie

et al. 2010

Biological & Pharmaceutical Bulletin

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Licorice extracts and the principal licorice component glycyrrhizin (GL) are used worldwide in foods, tobacco and medicines. The sweet taste of licorice roots arises from GL, which is reputed to be at least 50 times sweeter than refined sugar. Owing to this sweetness, GL is extensively used as a natural sweetener and flavoring additive.1) GL is a saponin compound comprising a triterpenoid aglycone, glycyrrhetinic acid (GA), conjugated to a disaccharide of glucuronic acid. GA is used as an antitoxic and immunological regulatory agent for the prevention or treatment of viral infection, inflammation and anaphylaxis.2,3) However, despite its wide use in the market and great effects on some physiological aspects, to the best of our knowledge, no studies have investigated the antitumor effects of GA on tumor cells in the central nervous system (CNS).Serum-free mouse embryo (SFME) cells were originally derived from a 16-d-old whole Balb/c mouse embryo and are maintained in a serum-free culture medium.4) These cells do not undergo growth crisis, maintain their diploid karyotype for extended passages and are non-tumorigenic in vivo. Consequently, they are non-transformed, behave as primary cultures, have a finite lifespan and display the characteristics of CNS progenitor cells.5,6) SFME cells were cotransfected with the human c-Ha-ras and mouse c-myc genes, and the resulting cells were designated ras/myc SFME cells. 7) While SFME cells are non-tumorigenic in vivo, 5,6) ras/myc SFME cells are tumorigenic and do not require any growth factors, such as epidermal growth factor. 7) Another line of SFME-derived tumorigenic cells are highly metastatic ras/myc SFME-1 (r/m HM-SFME-1) cells, which were established by selecting ras/myc SFME cells that only metastasize to the lungs of Balb/c mice. 8) In the present study, r/m HM-SFME-1 cells were treated with GA and its efficacy as an antitumor agent through anoikis-like cell death and cytoskeletal disruption was investigated. Cell Culture SFME and r/m HM-SFME-1 cells were cultured in a humidified 5% CO 2 -95% air atmosphere at 37°C in 60 mm diameter dishes, pre-coated with 10 mg/ml fibronectin. The basal nutrient culture medium was a 1 : 1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 9,10) containing 15 mM N-(2-hydroxyethyl)piperazine-NЈ-2-ethanesulfonic acid (HEPES), pH 7.4, 1.2 mg/ml sodium bicarbonate, 10 nM sodium selenite and 10 mg/ml gentamicin, supplemented with insulin (10 mg/ml), transferrin (25 mg/ml) and epidermal growth factor (50 ng/ml). Cell passages were accomplished by rapid trypsinization with 0.2% crude trypsin and 1 mM ethylenediaminetetraacetate in phosphatebuffered saline (PBS) without calcium or magnesium, followed by dilution in the culture medium at room temperature. The medium containing the collected cells was centrifuged at 250 g at 4°C for 7 min and the supernatant was removed. The cells were suspended in the culture medium without the supplements, plated at 1ϫ10 5 cells/dish and cultured again in the medium with the supplements. Following...

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“…However, our previous study revealed the potential involvement of Ras in the selective toxicity by GA against the tumor cells (3). Ras pathways have been targeted for the development of chemotherapeutic interventions against tumor cells by interfering with cytoskeletal proteins such as actin (31) and tubulin (43). Furthermore, in our previous (44,45) and current studies, we found that GA disrupted F-actin and ␤III-tubulin, which could lead to loss of functionality for cell growth or proliferation and result in apoptosis of the cells.…”

Section: Discussionmentioning

confidence: 99%

“…5B and supplemental Movie S2), suggesting that GA could disrupt cytoskeletal proteins because they provide the cell shape and maintain the cellular structure (31). Therefore, the tumor cells were treated with GA at 10 M for 24 h, and the effects on F-actin and ␤III-tubulin in the cells were analyzed.…”

Section: Time-lapse Microscopy For Ga-treated Tumormentioning

confidence: 99%

Ligand-receptor Interaction between Triterpenoids and the 11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) Enzyme Predicts Their Toxic Effects against Tumorigenic r/m HM-SFME-1 Cells

Yamaguchi

Tang

Noshita

et al. 2011

Journal of Biological Chemistry

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The present study deals with in silico prediction and in vitro evaluation of the selective cytotoxic effects of triterpenoids on tumorigenic human c-Ha-ras and mouse c-myc cotransfected highly metastatic serum-free mouse embryo-1 (r/m HM-SFME-1) cells. Ligand fitting of five different triterpenoids to 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2) was analyzed with a molecular modeling method, and glycyrrhetinic acid (GA) was the best-fitted triterpenoid to the ligand binding site in 11␤HSD2. Analysis of antiproliferative effects revealed that GA, oleanolic acid, and ursolic acid had selective toxicity against the tumor cells and that GA was the most potent triterpenoid in its selectivity. The toxic activity of the tested triterpenoids against the tumor cells showed good correlations with the partition coefficient (logP) and polar surface area values. Time-lapse microscopy, fluorescence staining, and confocal laser scanning microscopic observation revealed that GA induced morphologic changes typical of apoptosis such as cell shrinkage and blebbing and also disrupted the cytoskeletal proteins. Furthermore, GA exhibited a strong inhibitory effect on 11␤HSD2 activity in the tumor cells. Our current results suggest that analysis of the ligand-receptor interaction between triterpenoids and 11␤HSD2 can be utilized to predict their antitumor effects and that GA can be used as a possible chemopreventive and therapeutic antitumor agent. To the best of our knowledge, this is the first report on in silico prediction of the toxic effects of triterpenoids on tumor cells by 11␤HSD2 inhibition.Triterpenoids, which are biosynthesized in plants by cyclization of squalene, are widely distributed throughout the vegetable kingdom, utilized in many food products and the major components of medicinal plants used in Asian countries (1). There is a growing interest in elucidating the biological and pharmacological roles of triterpenoids in analgesic, anti-inflammatory, anti-tumor, hepatoprotective, and immunomodulatory effects (1), and we have been focusing our attention on certain triterpenoids as multifunctional agents for the prevention and treatment of cancer. Recently, we found that ursolic acid (UA) 2 from apples was selectively toxic to tumorigenic human c-Ha-ras and mouse c-myc cotransfected highly metastatic serum-free mouse embryo-1 (r/m HM-SFME-1) cells (2). We further found that glycyrrhetinic acid (GA), a licorice component, was not only selectively toxic to the tumor cells but also more potent than some clinically available antitumor agents in its selectivity (3). SFME cells, which were established by Loo et al. (4), were originally derived from a 16-day-old whole Balb/c mouse embryo and are maintained in a serum-free culture medium. These cells do not undergo growth crisis, maintain their diploid karyotype for extended passages, and are non-tumorigenic in vivo. Consequently, they are non-transformed, behave as primary cultures, have a finite lifespan, and display the characteristics of the CNS progenitor cells (5, 6)....

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Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility

Cited by 23 publications

References 29 publications

Docetaxel suppresses invasiveness of head and neck cancer cells in vitro

Docetaxel suppresses invasiveness of head and neck cancer cells in vitro

Glycyrrhetinic Acid Induces Anoikis-Like Death and Cytoskeletal Disruption in the Central Nervous System Tumorigenic Cells

Ligand-receptor Interaction between Triterpenoids and the 11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) Enzyme Predicts Their Toxic Effects against Tumorigenic r/m HM-SFME-1 Cells

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