Antineoplastic Activity of Poly(L-lysine) with Some Ascites Tumor Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1979 Jul 1

PMID 291000

Citations 24

Authors

L J Arnold Jr

A Dagan

J Gutheil

N O Kaplan

Affiliations

Soon will be listed here.

Abstract

We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 x 10(3)) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells. White Swiss mice show nearly a 100% remission from subsequent tumor growth. Rechallenge of "cured" animals with tumor cells, however shows no long-term immunological protection. In tissue culture, poly(L-lysine) shows a related potent cytotoxicity with HeLa cells; interestingly, the D isomer. In addition, there is a strong molecular weight dependence in that the small polylysine (Mr 3 x 10(3)) possesses less than 1/20th the cytotoxicity of large polymers (Mr 70 x 10(3)) on a weight basis in both cell culture and animal studies. At the same time, none of these lysine polymers gives any significant increase in life span to BDF1 mice infected with L1210 murine leukemia cells. We have also further explored the mechanism by which the polylysines express their cytotoxicity. These data indicate that lysine polymers show cell specificity in their action and in some cases they may be beneficial as potent antineoplastic agents, particularly when molecular weight is taken into consideration.

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References

James A, AMBROSE E, LOWICK J . Differences between the electrical charge carried by normal and homologous tumour cells. Nature. 1956; 177(4508):576-7. DOI: 10.1038/177576a0. View

Shalitin C, KATCHALSKI E . Inactivation of Escherichia coli bacteriophage T2 by poly-L-lysine. II. Properties of the irreversibly inactivated phage. Arch Biochem Biophys. 1962; 99:508-16. DOI: 10.1016/0003-9861(62)90299-0. View

Kornguth S, STAHMANN M . Effect of polylysine on the leakage and retention of compounds by Ehrlich ascites tumor cells. Cancer Res. 1961; 21:907-12. View

Richardson T, HODGETT J, Lindner A, STAHMANN M . Action of polylysine on some ascites tumors in mice. Proc Soc Exp Biol Med. 1959; 101(2):382-6. DOI: 10.3181/00379727-101-24950. View

Berger A, Bichowsky-Slomnicki L, KATCHALSKI E, Kurtz J . The anti-bacterial action of some basic amino acid copolymers. Arch Biochem Biophys. 1956; 65(1):400-13. DOI: 10.1016/0003-9861(56)90201-6. View

Green M, STAHMANN M . Inhibition of mumps virus multiplication by a synthetic polypeptide. Proc Soc Exp Biol Med. 1953; 83(4):852-8. DOI: 10.3181/00379727-83-20514. View

Watson D, BLOOM W . Antimicrobial activity of a natural and a synthetic polypeptide. Proc Soc Exp Biol Med. 1952; 81(1):29-33. DOI: 10.3181/00379727-81-19769. View

De Vries A, FELDMAN J, Stein O, STEIN Y, KATCHALSKI E . Effects of intravenously administered poly-D L-lysine in rats. Proc Soc Exp Biol Med. 1953; 82(2):237-40. DOI: 10.3181/00379727-82-20078. View

RUBINI J, RASMUSSEN Jr A, STAHMANN M . Inhibitory effect of synthetic lysine polypeptides on growth of influenza virus in embryonated eggs. Proc Soc Exp Biol Med. 1951; 76(4):662-5. DOI: 10.3181/00379727-76-18588. View

10.

STAHMANN M, GRAF L, Patterson E, Walker J, Watson D . The inhibition of tobacco mosaic virus by synthetic lysine polypeptides. J Biol Chem. 1951; 189(1):45-52. View

11.

Seiler M, Rennke H, Venkatachalam M, COTRAN R . Pathogenesis of polycation-induced alterations ("fusion") of glomerular epithelium. Lab Invest. 1977; 36(1):48-61. View

12.

Ogawa K, Ichihara A . Inhibition of protein synthesis in mouse L cells by poly-L-ornithine. J Biochem. 1978; 83(2):519-25. DOI: 10.1093/oxfordjournals.jbchem.a131939. View

13.

Anghileri L, Heidbreder M, Mathes R . Accumulation of 57Co-poly-L-lysine by tumors: an effect of the tumor electrical charge. J Nucl Biol Med. 1976; 20(2):79-83. View

14.

Kawada J, Yoshimura Y, Minami T . Some properties of thyroidal membrane adenosinetriphosphatase and iodide uptake: effects of basic polyamino acids. Endocrinol Jpn. 1976; 23(3):221-5. DOI: 10.1507/endocrj1954.23.221. View

15.

RYSER H, Shen W . Conjugation of methotrexate to poly(L-lysine) increases drug transport and overcomes drug resistance in cultured cells. Proc Natl Acad Sci U S A. 1978; 75(8):3867-70. PMC: 392889. DOI: 10.1073/pnas.75.8.3867. View

16.

Schottler W, Bauer H . The PAL test for malignant disease in man. Br J Cancer. 1978; 37(2):319-21. PMC: 2009581. DOI: 10.1038/bjc.1978.42. View

17.

Lin S, Liao C, Lee C . Mechanism of anticholinesterase activities of cardiotoxin, protamine and polylysine. Biochem J. 1977; 161(2):229-32. PMC: 1164499. DOI: 10.1042/bj1610229. View

18.

McCoy G, Resch R, RACKER E . Characterization of dextran sulfate-treated ascites tumor cells and their repair by ascites fluid. Cancer Res. 1976; 36(9 pt.1):3339-45. View

19.

Duksin D, KATCHALSKI E, Sachs L . Specific aggregation of SV40-transformed cells by ornithine, leucine copolymers. Proc Natl Acad Sci U S A. 1970; 67(1):185-92. PMC: 283186. DOI: 10.1073/pnas.67.1.185. View

20.

Duksin D, Katchalski-Katzir E, Sachs L . Interaction of the basic copolymer - poly(ornithine, leucine with normal and transformed cells). FEBS Lett. 1975; 60(1):21-5. DOI: 10.1016/0014-5793(75)80409-1. View