Premium
Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies
Author(s) -
Tsai MinLing,
Yen ChengChieh,
Lu FungJou,
Ting HungChih,
Chang HorngRong
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22121
Subject(s) - arsenic trioxide , chemistry , in vivo , cell growth , reactive oxygen species , carcinogenesis , cancer research , pharmacology , biochemistry , apoptosis , biology , microbiology and biotechnology , gene
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.