Inhibition of human cancer cell lines in vitro with mono- and polynucleotides containing 5-mercaptocytosine bases.
Partially thiolated polycytidylic acid (5-mercaptopolycytidylic, MPC) and its double-stranded complex with polyinosinic acid [poly (I)].poly(I).MPC, were assayed in both antiproliferative and cytotoxicity tests against human cell lines: lung carcinoma A549, colon carcinoma HT-29, osteosarcoma HOS, and amnion cells (WISH). Inhibitory effects of MPC were noted in the antiproliferative assay with ID50 of 7, 24, 33, and 35 micrograms.ml-1, and in the cytotoxicity test with ID50 of 164, 174, 210, and 290 micrograms.ml-1 against the HOS, A549, HT-29, and WISH cells respectively. Comparison with the corresponding partially thiolated mononucleotide (5-mercapto-CMP + CMP) and the nucleoside (5-mercapto-cytidine) demonstrated that MPC was a more potent antiproliferative agent than either of its monomeric constituents. The inhibitory effect of MPC upon the incorporation of [3H]thymidine into the DNA of growing A549 cells paralleled its antiproliferative activity.
Geng
B Q
BQ
Department of Medicinal Chemistry, State University of New York, Buffalo 14260.
Ho
Y K
YK
Hughes
R G
RG
Bardos
T J
TJ
D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D012516:Osteosarcoma / Q000473:pathology; D011066:Poly C / Q000494:pharmacology*; D011069:Poly I / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C010218:5-mercaptopolycytidylic acid; D013873:Thionucleotides; D011069:Poly I; D011066:Poly C