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Published on: October 25, 2018
Inhibitory effect of selenite on invasion of HT1080 tumor cells
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
Abstract:
Selenium, an essential biological trace element, has been shown to reduce and prevent the incidence of cancer. Our previous studies have shown that selenite is involved in the chemoprevention of cancer and induction of apoptosis of cancer cells. In this study, we demonstrate that selenite also inhibits the invasion of tumor cells. Cancer cell invasion requires coordinated processes, such as changes in cell-cell and cell-matrix adhesion, degradation of the extracellular matrix, and cell migration. We found that selenite inhibited invasion of HT1080 human fibrosarcoma cells. Adhesion of HT1080 cells to the collagen matrix was also inhibited by treatment with selenite, but cell-cell interaction and cell motility were not affected by selenite. Moreover, selenite reduced expression of matrix metalloproteinase-2 and -9 and urokinase-type plasminogen activator, which are involved in matrix degradation, but increased a tissue inhibitor of metalloproteinase-1. This inhibitory effect of selenite on the protease expressions was mediated by the suppression of transcription factors, NF-kappaB and AP-1. However, selenate showed no remarkable effect on all the steps of cancer cell invasion.
Insights
Selenium supplementation, specifically selenite, inhibits cancer cell invasion by reducing matrix degradation and adhesion. Selenate did not show significant effects on cancer cell invasion processes.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Selenium is an essential trace element with known chemopreventive properties.
- Previous research indicates selenite's role in cancer chemoprevention and apoptosis induction.
- Cancer cell invasion is a critical step in metastasis, involving adhesion, matrix degradation, and migration.
Purpose of the Study:
- To investigate the effect of selenite on cancer cell invasion.
- To elucidate the mechanisms by which selenite affects invasion-related processes.
- To compare the effects of selenite and selenate on tumor cell invasion.
Main Methods:
- Treatment of HT1080 human fibrosarcoma cells with selenite.
- Assessment of cell invasion, adhesion to collagen, and cell motility.
- Analysis of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), urokinase-type plasminogen activator (uPA), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression.
- Evaluation of transcription factors NF-kappaB and AP-1 activity.
Main Results:
- Selenite significantly inhibited the invasion of HT1080 fibrosarcoma cells.
- Selenite reduced cell adhesion to the collagen matrix but did not affect cell-cell interaction or motility.
- Selenite decreased the expression of MMP-2, MMP-9, and uPA, while increasing TIMP-1 expression.
- The inhibitory effects of selenite on protease expression were mediated by the suppression of NF-kappaB and AP-1 transcription factors.
- Selenate demonstrated no significant impact on cancer cell invasion.
Conclusions:
- Selenite effectively inhibits cancer cell invasion and related matrix degradation.
- Selenite's mechanism involves downregulating key proteases (MMP-2, MMP-9, uPA) and upregulating inhibitors (TIMP-1) via NF-kappaB and AP-1 pathways.
- Selenite represents a potential therapeutic agent for preventing cancer metastasis, while selenate lacks similar efficacy.
