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Differential sensitivity of various human tumour-derived cell types to apoptosis by organic derivatives of selenium
Raxit J Jariwalla1, Bhakti Gangapurkar, Daniel Nakamura
1Laboratory of Viral, Immune and Malignant Diseases, California Institute for Medical Research, San Jose, CA 95128, USA. r.jariwalla@drrath.com
Abstract:
Selenium is an important trace element with anti-cancer properties. In the present study, the apoptosis-inducing effects of organic selenium derivatives, namely methyl-L-selenocysteine and selenomethionine, were evaluated in vitro on human tumour-derived cell lines from breast, liver, colon, brain, skin and a non-tumorigenic line of epithelial origin. Apoptosis was assessed by cell-death detection immunoassay on cytoplasmic cell lysates. Breast carcinoma cells were highly sensitive to the organic selenium compounds, manifesting apoptosis at concentrations as low as 0.113 microm (0.0205 microg/ml) selenium. By contrast, non-tumorigenic mammary epithelial cells displayed poor sensitivity to selenium, requiring a substantially high concentration of the trace element of 87.9 microm (16.0 microg/ml). The cell lines derived from hepatoma and neuroblastoma showed intermediate sensitivity, with colon carcinoma cells manifesting the lowest sensitivity to the trace element. These results indicate intrinsic differences in the sensitivity of human tumour derivatives to selenium-mediated apoptosis, providing experimental support for the development of organic selenium compounds as anti-neoplastic agents against solid tumours displaying selective apoptotic sensitivity to these compounds.
Insights
Organic selenium compounds like methyl-L-selenocysteine induce apoptosis in cancer cells. Breast cancer cells show high sensitivity, while non-tumorigenic cells require much higher selenium concentrations.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Selenium is a trace element with recognized anti-cancer properties.
- Organic selenium derivatives are being investigated for therapeutic potential.
Purpose of the Study:
- To evaluate the apoptosis-inducing effects of methyl-L-selenocysteine and selenomethionine.
- To assess the differential sensitivity of various human tumor cell lines to organic selenium compounds.
Main Methods:
- In vitro evaluation of organic selenium derivatives on human tumor cell lines (breast, liver, colon, brain, skin) and a non-tumorigenic epithelial line.
- Apoptosis assessment using cell-death detection immunoassay on cytoplasmic cell lysates.
Main Results:
- Breast carcinoma cells exhibited high sensitivity to organic selenium compounds, showing apoptosis at low concentrations (0.113 µM).
- Non-tumorigenic mammary epithelial cells displayed significantly lower sensitivity, requiring high concentrations (87.9 µM).
- Hepatoma and neuroblastoma cells showed intermediate sensitivity, while colon carcinoma cells were least sensitive.
Conclusions:
- Human tumor cell lines exhibit intrinsic differences in sensitivity to selenium-mediated apoptosis.
- Organic selenium compounds demonstrate potential as anti-neoplastic agents, particularly against tumors with selective apoptotic sensitivity.
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