Differential sensitivity of various human tumour-derived cell types to apoptosis by organic derivatives of selenium.
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.
Laboratory of Viral, Immune and Malignant Diseases, California Institute for Medical Research, San Jose, CA 95128, USA. r.jariwalla@drrath.com
Raxit J
RJ
Jariwalla
Bhakti
B
Gangapurkar
Daniel
D
Nakamura
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003545:Cysteine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000188:drug therapy / Q000473:pathology; D016566:Organoselenium Compounds / Q000627:therapeutic use; D018036:Selenium Compounds / Q000627:therapeutic use*; D017279:Selenocysteine / Q000031:analogs & derivatives; D012645:Selenomethionine / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D018036:Selenium Compounds; D017279:Selenocysteine; D012645:Selenomethionine; D003545:Cysteine; C002979:selenomethylselenocysteine