Induction of differentiation of Friend murine erythroleukemia cells by poly-L-lysine and daunorubicin-poly-L-lysine conjugate.
The ability of the synthetic cationic polypeptide poly-L-lysine (PLL) to induce differentiation of Friend murine erythroleukemia cells was examined with the use of polymers of different molecular weights. Like other membrane-interacting agents (polar solvents), all the polymers tested were effective in inducing cell differentiation. This effect was found to be molecular weight dependent, as already reported for other membrane-related actions of these polymers. Since anthracyclines also exert direct effects on the cell membrane, the activity of the daunorubicin-PLL conjugate was also examined. The covalent linking of the drug to the polyamino acid somewhat reduced the differentiation-inducing activity in this system. Indeed, free daunorubicin was found to inhibit the maturational process. Although the inducing effect was observed when the free PLL or daunorubicin-linked PLL was added alone, polymers enhanced differentiation produced by suboptimal concentrations of dimethyl sulfoxide (DMSO). Since PLL was inactive as an initiator of the maturation of a DMSO-resistant line, it is likely that some events (presumably membrane-related effects) involved in the multistep stimulation process are common to polar-planar solvents and the polycationic polymer.
Supino
R
R
Gibelli
N
N
Zunino
F
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003630:Daunorubicin / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D008970:Molecular Weight; D011107:Polylysine / Q000494:pharmacology*
D011107:Polylysine; D004121:Dimethyl Sulfoxide; D003630:Daunorubicin