Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies

ABSTRACT In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightl...

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Veröffentlicht in:Environmental toxicology 2016-09, Vol.31 (9), p.1121-1132
Hauptverfasser: Tsai, Min-Ling, Yen, Cheng-Chieh, Lu, Fung-Jou, Ting, Hung-Chih, Chang, Horng-Rong
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container_issue 9
container_start_page 1121
container_title Environmental toxicology
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creator Tsai, Min-Ling
Yen, Cheng-Chieh
Lu, Fung-Jou
Ting, Hung-Chih
Chang, Horng-Rong
description ABSTRACT In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121–1132, 2016.
doi_str_mv 10.1002/tox.22121
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However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. 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SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. 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subjects Animals
Apoptosis - drug effects
arsenic trioxide
Arsenicals
Cell Line, Tumor
Cell Movement - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Cervical cancer
Female
Glutathione - metabolism
HeLa Cells
human cervical cancer cells
Humans
humic acid
Humic Substances - toxicity
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 9 - metabolism
Mice
Mice, Inbred NOD
Mice, SCID
Mitosis - drug effects
Oxides - toxicity
Reactive Oxygen Species - metabolism
Transplantation, Heterologous
tumor progression
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
Vascular Endothelial Growth Factor A
title Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies
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