Steady-state messenger RNA and activity correlates with sensitivity to N1,N12-bis(ethyl)spermine in human cell lines representing the major forms of lung cancer.
Our previous results from a limited number of cell lines have suggested that the bis(ethyl)polyamine analogues exert a phenotype-specific response in human lung cancer cells. In the present study, we have extended this work to analyze the response of the 4 major forms of human lung cancer to the polyamine analogue N1,N12-bis(ethyl)spermine (BESpm). The results suggest that non-small cell phenotypes are much more sensitive to the cytotoxic effects of BESpm than the small cell lung carcinoma phenotype. Further, there appears to be a positive association between the level of induction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) in response to the analogue and the kinetic response of cells. Specifically, cells in which SSAT activity is highly induced by BESpm are killed by the compound. Although induction of SSAT appears to occur at both the level of increased steady-state mRNA and enzyme activity, SSAT activity appears to be a better indicator of cell sensitivity to BESpm than SSAT mRNA levels. These results have significance both for the potential use of polyamine analogues in treating specific forms of human lung cancer and for understanding the regulation of SSAT at the molecular level.
Casero
R A
RA
Johns Hopkins University School of Medicine Oncology Center, Baltimore, Maryland 21231.
Mank
A R
AR
Xiao
L
L
Smith
J
J
Bergeron
R J
RJ
Celano
P
P
D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004790:Enzyme Induction; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D010641:Phenotype; D011073:Polyamines / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012680:Sensitivity and Specificity; D013096:Spermine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D011073:Polyamines; D012333:RNA, Messenger; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C052614:N(1), N(12)-diethylspermine