Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins.

Abstract	The plant alkaloid camptothecin and three camptothecin derivatives were used to study responses of human malignant melanoma (BRO) cells xenografted in immunodeficient (nude) mice. Camptothecin and its derivatives 9-nitro-20(S)-camptothecin and 9-amino-20(S)-camptothecin inhibited growth of tumors and caused regression in all tumor-bearing mice. Tumor regression was accompanied by degenerative changes in the tumor cells, as assessed by microscopic observations of histological sections prepared from the tumors. No toxic effects were observed in the drug-treated mice, with or without xenografts. In parallel experiments, camptothecin, 9-nitro-20(S)-camptothecin, and 9-amino-20(S)-camptothecin inhibited proliferation of BRO cells in vitro and resulted in dramatic morphological cellular changes comparable to those observed in the sections of solid tumors. The derivative 12-nitro-20(S)-camptothecin had no effect on BRO tumors or cell cultures. The difference between 9-nitro-20(S)-camptothecin and 12-nitro-20(S)-camptothecin is the position at which the NO2 group is attached to the camptothecin molecule. In contrast to BRO melanoma cells, none of the camptothecin derivatives had any effect on cultured human melanocytes, the normal counterparts of melanoma cells. Taken together, the findings indicate that camptothecin and derivatives exert different effects on the growth and morphology of normal and malignant (BRO) melanocytes.
Authors	P Pantazis, H R Hinz, J T Mendoza, A J Kozielski, L J Williams Jr, J S Stehlin Jr, B C Giovanella
Journal	Cancer research (Cancer Res) Vol. 52 Issue 14 Pg. 3980-7 (Jul 15 1992) ISSN: 0008-5472 [Print] United States
PMID	1617674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Camptothecin
Topics	Animals Body Weight (drug effects) Camptothecin (analogs & derivatives, pharmacology) Cell Death Cell Division (drug effects) Drug Screening Assays, Antitumor Graft Survival (drug effects) Male Melanoma (drug therapy, pathology) Mice Mice, Nude Neoplasm Transplantation Remission Induction Tumor Cells, Cultured

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