Polysaccharides from green sweet pepper increase the antineoplastic effect of methotrexate on mammary tumor cells

This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously in...

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Vydané v:	International journal of biological macromolecules Ročník 158; s. 1071 - 1081
Hlavní autori:	Adami, Eliana Rezende, Corso, Claudia Rita, Turin-Oliveira, Natalia Mulinari, Galindo, Claudia Martins, Milani, Leticia, Stipp, Maria Carolina, da Silva, Liziane Cristine Malaquias, do Nascimento, Georgia Erdmann, Chaves, Pedro Felipe Pereira, Chequin, Andressa, Mariott, Marihá, da Silva, Luisa Mota, Klassen, Giseli, Ramos, Edneia A.S., Cordeiro, Lucimara M.C., Acco, Alexandra
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 01.09.2020
Predmet:	angiogenesis Breast tumor Capsicum annuum cell viability drug therapy females gene expression human cell lines inflammation interleukin-10 interleukin-4 interleukin-6 Interleukins laboratory animals mammary neoplasms (animal) methotrexate mice necrosis neoplasm cells polysaccharides sweet peppers toxicity tumor necrosis factor-alpha Interleukins Capsicum annuum Breast tumor
ISSN:	0141-8130, 1879-0003, 1879-0003
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Abstract	This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg−1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg−1 CAP (p.o.) + 1 mg kg−1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg−1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity. •Long treatment with polysaccharides from sweet green pepper (CAP) has antineoplastic effect.•CAP and CAP + methotrexate (MTX) treatment modulate inflammation and angiogenesis in tumor microenvironment.•CAP increases the effects of MTX in mammary tumor cells from human and mice.
AbstractList	This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg−1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg−1 CAP (p.o.) + 1 mg kg−1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg−1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity. •Long treatment with polysaccharides from sweet green pepper (CAP) has antineoplastic effect.•CAP and CAP + methotrexate (MTX) treatment modulate inflammation and angiogenesis in tumor microenvironment.•CAP increases the effects of MTX in mammary tumor cells from human and mice. This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg-1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg-1 CAP (p.o.) + 1 mg kg-1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg-1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity.This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg-1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg-1 CAP (p.o.) + 1 mg kg-1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg-1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity. This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg , p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg CAP (p.o.) + 1 mg kg MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg , i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity. This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg⁻¹, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg⁻¹ CAP (p.o.) + 1 mg kg⁻¹ MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg⁻¹, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity.
Author	Mariott, Marihá Klassen, Giseli Galindo, Claudia Martins Chaves, Pedro Felipe Pereira Chequin, Andressa Acco, Alexandra Adami, Eliana Rezende Stipp, Maria Carolina Milani, Leticia do Nascimento, Georgia Erdmann Turin-Oliveira, Natalia Mulinari da Silva, Liziane Cristine Malaquias Corso, Claudia Rita da Silva, Luisa Mota Cordeiro, Lucimara M.C. Ramos, Edneia A.S.
Author_xml	– sequence: 1 givenname: Eliana Rezende surname: Adami fullname: Adami, Eliana Rezende organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 2 givenname: Claudia Rita surname: Corso fullname: Corso, Claudia Rita organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 3 givenname: Natalia Mulinari surname: Turin-Oliveira fullname: Turin-Oliveira, Natalia Mulinari organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 4 givenname: Claudia Martins surname: Galindo fullname: Galindo, Claudia Martins organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 5 givenname: Leticia surname: Milani fullname: Milani, Leticia organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 6 givenname: Maria Carolina surname: Stipp fullname: Stipp, Maria Carolina organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 7 givenname: Liziane Cristine Malaquias surname: da Silva fullname: da Silva, Liziane Cristine Malaquias organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 8 givenname: Georgia Erdmann surname: do Nascimento fullname: do Nascimento, Georgia Erdmann organization: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 9 givenname: Pedro Felipe Pereira surname: Chaves fullname: Chaves, Pedro Felipe Pereira organization: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 10 givenname: Andressa surname: Chequin fullname: Chequin, Andressa organization: Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 11 givenname: Marihá surname: Mariott fullname: Mariott, Marihá organization: Postgraduate Program in Pharmaceutical Sciences, University Vale of Itajaí, Itajaí, SC, Brazil – sequence: 12 givenname: Luisa Mota surname: da Silva fullname: da Silva, Luisa Mota organization: Postgraduate Program in Pharmaceutical Sciences, University Vale of Itajaí, Itajaí, SC, Brazil – sequence: 13 givenname: Giseli surname: Klassen fullname: Klassen, Giseli organization: Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 14 givenname: Edneia A.S. surname: Ramos fullname: Ramos, Edneia A.S. organization: Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 15 givenname: Lucimara M.C. surname: Cordeiro fullname: Cordeiro, Lucimara M.C. organization: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 16 givenname: Alexandra surname: Acco fullname: Acco, Alexandra email: aleacco@ufpr.br organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
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Keywords	Interleukins Capsicum annuum Breast tumor
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SubjectTerms	angiogenesis Breast tumor Capsicum annuum cell viability drug therapy females gene expression human cell lines inflammation interleukin-10 interleukin-4 interleukin-6 Interleukins laboratory animals mammary neoplasms (animal) methotrexate mice necrosis neoplasm cells polysaccharides sweet peppers toxicity tumor necrosis factor-alpha
Title	Polysaccharides from green sweet pepper increase the antineoplastic effect of methotrexate on mammary tumor cells
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