Dergiler / Turkish Journal of Cancer / 2000 / Cilt: 30 - Sayı: 3
Polyamine drug inhibition of the proliferation of a small cell lung cancer cell line NIH-H82 with amplified myc oncogene
- Sayfa
- 97–104
- DOI
- —
Özet
Small cell lung carcinoma (SCLC) compromises rapidly proliferating, highly metastatic cancer cells leading to a negative prognosis for the patient. All such cells have elevated levels of polyamines and amplified myc oncogene expression. In the current study we evaluated the effects of two polyamine synthesis inhibitors (DFMO and methyl GAG) and two polyamine analogues (BE4-4-4-4 and BEPUT) on the cellular proliferation and polyamine levels in a human SCLC cell line (NCI-H82) which contained 25 fold elevated levels of both c-myc DNA and RNA. Individually, BE4-4-4-4 and BEPUT, showed 40% and 55% inhibition of cell proliferation, and gave 15% and 17% decrease in polyamine levels. However, when BE4-4-4-4-4 and BEPUT were simultaneously incubated with the SCLC cells, proliferation was inhibited 98%, while only a 20% decrease in polyamine levels occurred. BE4-4-4-4 and BEPUT have recently been reported to prevent/inhibit polyamine activation of casein kinase II, which activates both ornithine decarboxylase and myc oncoprotein via serine phosphorylations. It is possible that the above observed inhibition of SCLC cell proliferation may be related to specific, not general polyamine functioning, and probably involves more than one molecular target.
Abstract
Small cell lung carcinoma (SCLC) compromises rapidly proliferating, highly metastatic cancer cells leading to a negative prognosis for the patient. All such cells have elevated levels of polyamines and amplified myc oncogene expression. In the current study we evaluated the effects of two polyamine synthesis inhibitors (DFMO and methyl GAG) and two polyamine analogues (BE4-4-4-4 and BEPUT) on the cellular proliferation and polyamine levels in a human SCLC cell line (NCI-H82) which contained 25 fold elevated levels of both c-myc DNA and RNA. Individually, BE4-4-4-4 and BEPUT, showed 40% and 55% inhibition of cell proliferation, and gave 15% and 17% decrease in polyamine levels. However, when BE4-4-4-4-4 and BEPUT were simultaneously incubated with the SCLC cells, proliferation was inhibited 98%, while only a 20% decrease in polyamine levels occurred. BE4-4-4-4 and BEPUT have recently been reported to prevent/inhibit polyamine activation of casein kinase II, which activates both ornithine decarboxylase and myc oncoprotein via serine phosphorylations. It is possible that the above observed inhibition of SCLC cell proliferation may be related to specific, not general polyamine functioning, and probably involves more than one molecular target.