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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Selenium and signal transduction: roads to cell death and anti-tumour activity
A Ghose1, J Fleming, P R Harrison
1CRC Beatson Laboratories, The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
Abstract:
Accumulated evidence from prospective studies, intervention trials and studies on animal models of cancer have suggested a strong inverse correlation between selenium intake and cancer incidence. Several putative mechanisms have been suggested to mediate the chemopreventive activities of selenium: of these, the inhibition of cellular proliferation and the induction of apoptosis are particularly attractive. The mitogen activated protein kinase (MAPK) pathways are known to be important regulators of cell death and our recent work has focused on the involvement of these pathways in selenium-induced apoptosis in primary cultures of oral cancers and corresponding normal mucosa derived from biopsy material. Using this system, the oral carcinoma cells were found to have enhanced sensitivity to apoptosis when treated with certain selenium compounds compared to normal oral mucosa. Induction of Fas ligand was associated with selenium-induced apoptosis. Signal transduction studies suggests that selenium induces several changes in the MAPK signalling pathways but functional intervention/inhibitor studies indicate that activation of the JNK pathway seems to be most important.
Insights
Selenium compounds may prevent oral cancer by inducing apoptosis, or programmed cell death, in cancer cells. This process involves the c-Jun N-terminal kinase (JNK) pathway, a key regulator of cell death.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Growing evidence suggests a link between selenium intake and reduced cancer incidence.
- Selenium's potential chemopreventive effects are attributed to mechanisms like inhibiting cell proliferation and inducing apoptosis.
- Mitogen-activated protein kinase (MAPK) pathways are critical regulators of cell death.
Purpose of the Study:
- To investigate the role of MAPK pathways in selenium-induced apoptosis in oral cancer.
- To compare the sensitivity of oral carcinoma cells and normal oral mucosa to selenium compounds.
Main Methods:
- Primary cultures of oral cancer cells and normal oral mucosa from biopsy material were used.
- Cells were treated with specific selenium compounds.
- Apoptosis induction, Fas ligand expression, and MAPK pathway activation (including JNK) were analyzed.
Main Results:
- Oral carcinoma cells exhibited increased sensitivity to apoptosis upon treatment with certain selenium compounds compared to normal oral mucosa.
- Selenium-induced apoptosis was associated with the induction of Fas ligand.
- Signal transduction studies revealed alterations in MAPK pathways, with JNK pathway activation being crucial for selenium's apoptotic effect.
Conclusions:
- Selenium compounds demonstrate potential in inducing apoptosis specifically in oral cancer cells.
- The JNK pathway plays a significant role in mediating selenium-induced apoptosis in oral cancer.
- These findings support selenium's chemopreventive potential against oral cancer.
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