Summary
The combination of mitoxantrone with lucanthone, a schistosomicidal and nonmyelotoxic agent, yielded a therapeutic synergism in L 1210 and P 388 leukemia with no increase in toxicity. In that combination the nonmyelotoxic lucanthone enabled the use of the optimal dose of mitoxantrone. The recent hypothesis that planar polycyclic aromatic compounds, mostly comprised by the term intercalators, intercalate with DNA or bind to DNA may need receiving with respect to membrane target sites.
Similar content being viewed by others
References
Blanc JE Jr, French FA (1963) A systematic investigation of thioxanthen-9-ones and analogues as potential antitumor agents. J Med Chem 6:185–191
Bowden GT, Peng YM, Alberts DsS (1984) Comparative molecular pharmacology of the anthracene anti-cancer drugs bisantrene and mitoxantrone. Proc Ann Meet Am Assoc Cancer Res 25:265
Corbett TH, Roberts BJ, Trader MW, Laster WR Jr, Griswold DP Jr, Schabel FM Jr (1982) Response of transplantable tumors of mice to anthracenedione derivatives alone and in combination with clinically useful agents. Cancer Treat Rep 66:1187–1200
Croisy-Delcey M, Bisagni E (1983) Aza analogues of lucanthone: synthesis and antitumor and bactericidal properties. J Med Chem 26:1329–1333
Durr FE (1984) Biologic and biochemical effects of mitoxantrone. Semin Oncol 11:3–10
Durr FE, Wallace RE, Citarella RV (1983) Molecular and biochemical pharmacology of mitoxantrone. Cancer Treat Rev 11:3–11
Fujimoto S, Ogawa M (1982) Antitumor activity of mitoxantrone against murine experiment tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol 8:157–162
Hackmann C, Gönnert R, Mauss H (1949) Untersuchungen über die tumorhemmende Wirkung des Miracils. Naturwissenschaften 36:29
Hickman JA, Scanlon KJ, Tritton TR (1984) Membrane targets in cancer chemotherapy. Trends in Pharmacol Sci 5:15–17
Hirschberg E, Gellhorn A, Murray MR, Elslager F (1959) Effects of miracil D, amodiaquin, and a series of other 10-thiaxanthenones and 4-aminoquinolines against a variety of experimental tumors in vitro and in vivo. J Natl Cancer Inst 22:567–579
Iigo M, Kanzawa F, Nakamura A, Hoshi A, Kuretani K (1977) Interaction of antitumor agents including doxorubicin or daunorubicin sarcoma-180 system. Gann 68:459–467
Johnson RK, Zee-Cheng RKY, Lee WW, Acton EM, Henry DH, Cheng CC (1979) Experimental antitumor activity of aminoanthraquinones. Cancer Treat Rep 63:425–439
Kapuscinski J, Darzynkiewicz Z, Traganos F, Melamed MR (1981) Interactions of a new antitumor agent, 1,4-dihydroxy-5,8-bis//2-/(2-hydroxyethyl)amino/-ethyl/amino/-9,10-anthracence-dione with nucleic acids. Biochem Pharmacol 30:231–240
Kharasch ED, Novak RF (1982) Inhibition of adriamycin stimulated microsomal lipid peroxidation by mitoxantrone and ametantrone, two new anthracenedione antineoplastic agents. Biochem Biophys Res Comm 108:1346–1352
Murdock KC, Child RG, Fabio PF, Angier RB, Wallace RE, Durr FE, Citarella RW (1979) Antitumor agents. 1. 1,4-bis/(aminoalkyl)amino/-9,10-anthracenediones. J Med Chem 22:1024–1030
Tritton TE, Yee G (1982) The anticancer agent can be actively cytotoxic without entering cells. Science 217:248–250
Wallace RE, Murdock KC, Angier RB, Durr FE (1979) Activity of a novel anthracenedione, 1,4-dihydroxy-5,8-bis 2-/2-hydroxyethyl)amino/ethyl amino-9,10-anthracenedione dihydrochloride, against experimental tumors in mice. Cancer Res 39:1570–1574
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday
Rights and permissions
About this article
Cite this article
Osswald, H., Youssef, M. Overadditive synergism between the intercalators mitoxantrone and lucanthone in advanced L 1210 and P 388 leukemia. J Cancer Res Clin Oncol 111, 137–140 (1986). https://doi.org/10.1007/BF00400752
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00400752