Combined therapy with disintegrin and melphalan as a new strategy in inhibition of endometrial cancer cell line (Ishikawa) growth.

Miltyk, Wojciech; Surażyński, Arkadiusz; Wołczyński, Sławomir; Pałka, Jerzy

doi:10.2478/v10042-009-0051-x

Cited by 5 publications

(8 citation statements)

References 28 publications

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“…The functional significance of the treatment of MDA-MB-231 breast cancer cells cisplatin plus echistatin was found also at the level of collagen biosynthesis. Our findings are consistent with the previous work which demonstrated that combination therapy with cytostatic agents from the group of alkylating agents and echistatin, produces a greater decrease in collagen biosynthesis than treatment with the alkylating drug alone [ 47 ]. Decreased amount of collagen in extracellular matrix may facilitate motility and invasion of neoplastic cells, but also may suppress cell growth and induce of apoptosis [ 48 ] as confirmed our results.…”

Section: Discussionsupporting

confidence: 93%

“…The same effect was achieved by echistatin—β 1 -integrin blocker [ 51 ]. The endometrial cancer cells treated for 24 h with melphalan and disintegrin showed decreased expression of IGF receptor in comparison to the cells treated with both compounds separately [ 47 ]. Our study showed that treatment cisplatin plus echistatin inhibited expression of that receptor more than cisplatin alone.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

et al. 2016

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The aim of our study was to determine whether the use of cisplatin in the presence echistatin in MDA-MB-231 breast cancer cells leads to a reduction of toxic effects associated with the use of cisplatin. The expression of β1-integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: protein kinase B (AKT), mitogen-activated protein kinases (ERK1/ERK2), nuclear factor kappa B (NFκB), and caspase-3 and -9 activity was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The viability of MDA-MB-231 breast cancer cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Annexin V-FITC/propidium iodide staining assay was performed to detect the induction of apoptosis. Inhibition DNA biosynthesis was determined by [3H]thymidine incorporation into DNA. The expression of of β1-integrin, IGF-IR, AKT, ERK1/ERK2, NFκB, caspase-3 and -9 was evaluated using Western blot. The results suggest that treatment of MDA-MB-231 breast cancer cells for 24 h cisplatin plus echistatin severely inhibits cell growth and activates apoptosis by upregulation of caspase-3 and -9 expressions. The effect was stronger than treatment cisplatin and echistatin alone. In this study, we have found that cisplatin plus echistatin treatment decreases collagen biosynthesis in MDA-MB-231 breast cancer cells stronger than the individual compounds. The inhibition was found to be dependent on the β1-integrin and IGF receptor activation. A significant reduction of ERK1/ERK2, AKT expression in cancer cells after cisplatin plus echistatin treatment was also found. The cancer cells treated by echistatin, cisplatin, and in particular the combination of both compounds drastically increased expression of NFκB transcription factor. Our results suggest that combined therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin. This mechanism probably is due to downregulation of expression of β1-integrin and IGF-IR receptors, and the signaling pathway proteins induced by these receptors. Our results suggest that therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

et al. 2016

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“…In fact, it has been documented previously that coupling of insulin-like growth factor receptor and thrombin-activated β1-integrin receptor signaling augmented proliferation and collagen biosynthesis in different cell types 45. In contrast, disintegrins were found to suppress both processes 46,47. Therefore, we suggest that in contrast to SPRP and SActi-PRP, the PRP contains ligands for integrin receptors, for example, thrombin.…”

Section: Discussionmentioning

confidence: 59%

“… 45 In contrast, disintegrins were found to suppress both processes. 46 , 47 Therefore, we suggest that in contrast to SPRP and SActi-PRP, the PRP contains ligands for integrin receptors, for example, thrombin. However, the identification of specific protein in PRP that is involved in the upregulation of integrin signaling is of particular interest and requires further studies.…”

Section: Discussionmentioning

confidence: 90%

Differential effect of platelet-rich plasma fractions on β1-integrin signaling, collagen biosynthesis, and prolidase activity in human skin fibroblasts

Guszczyn¹,

Surażyński²,

Zaręba³

et al. 2017

DDDT

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The study was conducted to evaluate the effects of platelet-rich plasma (PRP), supernatant of PRP (SPRP) obtained by centrifugation, and supernatant of activated PRP (SActi-PRP) obtained by Ca2+ solution-treated PRP on collagen biosynthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. Incubation of fibroblasts with 5% PRP for 24 h contributed to ~5-fold increase in collagen biosynthesis compared to the control. In the cells treated with 5% of SPRP or SActi-PRP, collagen biosynthesis showed a 3-fold increase of the control. PRP, SPRP, and SActi-PRP stimulated prolidase activity similar to collagen biosynthesis. Collagen biosynthesis and prolidase activity are regulated by β1-integrin receptor signaling. Incubation of fibroblasts with PRP for 24 h contributed to a dose-dependent increase in the expression of β1-integrin receptor, while SActi-PRP increased the process to a much lower extent. SPRP had no effect on the β1-integrin receptor expression. All the studied fractions of blood increased the expression of FAK as well as the expression of phosphorylated MAP-kinases. However, PRP was found to be the most effective stimulator of expression of these particular kinases. These studies suggest that a complex of factors, including growth factors, adhesion molecules, and prolidase contained in PRP, all evoke growth and collagen-promoting activities in human dermal fibroblasts.

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“…En las células T24, de carcinoma de vejiga humana, su unión a la integrina αVβ3 inhibe la adhesión a láminas de fibronectina y también desprende la fibronectina de células GD25 de ratón induciendo su apoptosis por medio de la disminución de los eventos de fosforilación en la vía FAK (15,20) .…”

Section: Desintegrinas Ofídicas Y Sus Potenciales Propiedades Anticanunclassified

Uso potencial de componentes del veneno de serpiente en el tratamiento del cáncer

Vivas

Inga

Yarlequé

2012

Rev Peru Med Exp Salud Publica

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INTRODUCCIÓNLas células cancerígenas reestructuran vías completas de señalización metabólica que permiten su proliferación ilimitada; los requerimientos para su superviviencia, migración e invasividad dependen de la participación de variadas moléculas (factores de crecimiento, integrinas), y de la interacción con otras células y la matriz extracelular (MEC). Las terapias contra el cáncer se centran en la búsqueda de moléculas antogonistas que impidan las interacciones de las células neoplásicas con su entorno (bloqueando su proliferación, su migración, e induciendo su apoptosis) (1,2) . El presente artículo da a conocer el papel que poseen las desintegrinas ofídicas como potenciales inhibidores de la angiogénesis y la metástasis. LA ANGIOGÉNESIS Y LA METÁSTASISLa angiogénesis es un proceso esencial altamente regulado que normalmente se da en eventos de desarrollo embrionario, crecimiento y reparación de heridas. Sin embargo, en un desarrollo tumoral, este proceso se torna continuo permitiendo el suministro de oxígeno y nutrientes (1) .Un tumor induce la angiogénesis cuando sus células, en un estado de hipoxia, producen una molécula conocida el factor alfa hipoxia inducible (HIF-α) que estimula la producción del factor de crecimiento de endotelio vascular A (VEGF-A), activador angiogénico mejor conocido a la fecha (2,3) . Este activador se une USO POTENCIAL DE COMPONENTES DEL VENENO DE SERPIENTE EN EL TRATAMIENTO DEL CÁNCERDan Vivas 1,a , Rosío Inga 1,2,a , Armando Yarlequé 1,b . RESUMENEl desarrollo del cáncer es posible en la medida que las células tumorales proliferen, se dispersen e invadan otros tejidos del cuerpo. Las integrinas son una familia de receptores heterodiméricos de superficie celular que cumplen un papel crucial en el desarrollo de la angiogénesis, crecimiento y metástasis de un tumor señalándolas como un atractivo blanco terapéutico. Los venenos de serpientes contienen péptidos de bajo peso molecular conocidos como desintegrinas, las que se unen con una alta afinidad a las integrinas e inhiben su accionar en un proceso cancerígeno. En el siguiente articulo revisamos los resultados de investigaciones, tanto in vitro como in vivo, que han mostrado resultados promisorios, por lo cual el uso de las desintegrinas podrían constituir una alternativa promisoria para el tratamiento de diversas neoplasias.Palabras clave: Cáncer; Venenos de serpiente; Desintegrinas; Tratamiento (fuente: DeCS BIREME). POTENTIAL USE OF SNAKE VENOM COMPONENTS IN CANCER TREATMENT ABSTRACTCancer can develop to the extent tumor cells grow, divide and grow into other body tissues. Integrins are a family of cell-surface heterodimeric receptors that play an important role in the development of tumor angiogenesis, growth and metastasis, thus being recognized as an attractive therapeutic target. Snake venom contains low-molecular weight peptides known as "disintegrins" that bind to integrins with high affinity, and prevent their action in cancer. In the next article, we go over the results of investigations, both in vitro and in viv...

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Combined therapy with disintegrin and melphalan as a new strategy in inhibition of endometrial cancer cell line (Ishikawa) growth.

Cited by 5 publications

References 28 publications

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

Differential effect of platelet-rich plasma fractions on β1-integrin signaling, collagen biosynthesis, and prolidase activity in human skin fibroblasts

Uso potencial de componentes del veneno de serpiente en el tratamiento del cáncer

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Combined therapy with disintegrin and melphalan as a new strategy in inhibition of endometrial cancer cell line (Ishikawa) growth.

Cited by 5 publications

References 28 publications

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

Differential effect of platelet-rich plasma fractions on &beta;1-integrin signaling, collagen biosynthesis, and prolidase activity in human skin fibroblasts

Uso potencial de componentes del veneno de serpiente en el tratamiento del cáncer

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Differential effect of platelet-rich plasma fractions on β1-integrin signaling, collagen biosynthesis, and prolidase activity in human skin fibroblasts