Abstract:
The effects of harringtonine, homoharringtonine, isoharringtonine and deoxyharringtonine on the biosynthesis of proteins in leukemias L-615 and P-388 were studied.The results indicate that the inhibitory effects of harringtonine, homoharringtonine, isoharringtonine and deoxyharringtonine on the incorporation of radioactive labelled amino acids into proteins of the spleen of mice bearing transplantable leukemia L-615 and into protein of leukemia P-388 cells
in vivo were very significant. When 1/5 of the LD
50 was injected into mice bearing leukemias L-615 and P-388 intraperitoneally or intravenously, respectively, the incorporation rates of
14C-DL-phenylanine or
3H-L-asparagine were reduced thirty minutes after single injection of the four alkaloids. Maximal inhibition was observed thirty minutes to 4 hours after drug administration and recovered after 24 hours. Generally the inhibitory effects of the four alkaloids was similar in terms of the time-effect curve. Even if 1/20 of LD
50 dose was used intraperitoneally, the inhibitory effect on
3H-DL-leucine incorporation by the four alkaloids in leukemia P-388 was still significant. It is very interestingthat harringtonine can not markedly influence the incorporation of
14C-DL-phenylalanine into the protein of the spleen of leukemic mice 24 hours after the last dose of five consecutive doses. It is suggested that the inhibitory effects of the four alkaloids on the incorporation of labelled amino acids into the protein of leukemic cells were significant, rapid and reversible.