Summary
The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i. v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adamovics JA, Hutchison CR (1979) Prodrug analogues of the antitumor alkaloid camptothecin. J Med Chem 22: 310
Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197: 893
Gallo RC, Jacqueline WP, Adamson RH (1971) Studies on the antitumor activity mechanism of action, and cell cycle effects of camptothecin. J Natl Cancer Inst 46: 789
Gottlieb JA, Luce JK (1972) Treatment of malignant melanoma with camptothecin (NSC-100880). Cancer Chemother Rep 56: 103
Gottlieb JA, Guarino AM, Call JB, Oliverio VT, Block JB (1970) Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chemother Rep 54: 461
Hart IR (1979) Selection and characterization of invasive variant of the B16 melanoma. Am J Pathol 97: 587
Muggia FM, Creaven PJ, Hansen HH, Cohen MH, Selawry OS (1972) Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): Correlation with preclinical studies. Cancer Chemother Rep 56: 515
Nagata H, Kaneda N, Furuta T, Sawada S, Yokokura T, Miyasaka T, Fukada M, Notake K (1988) Action of 7-ethylcamptothecin on tumor cells and its disposition in mice. Cancer Treat Rep 71: 341
Nitta K, Yokokura T, Sawada S, Takeuchi M, Tanaka T, Uehara N, Baba H, Kunimoto T, Miyasaka T, Mutai M (1985) Antitumor activity of a new derivative of camptothecin. In: Proceedings of the 14th International Congress on Chemotherapy, Kyoto, Japan, p 28
Schultz AG (1973) Camptothecin. Chem Rev 73: 385
Shamma M, Georgiev V (1974) Camptothecin. J Pharm Sci 63: 163
Tsou KC, Xu B, Miller EE, Lo KW (1981) Anti-tumor effect of (S)-10-hydroxycamptothecin on mouse hepatoma BW7756 and its possible mode of action. Anticancer Res 1: 115
Tsuruo T, Yamori T, Naganuma K, Tsukagoshi S, Sakurai Y (1983) Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26. Cancer Res 43:5437
Wall ME, Wani MC (1985) Antimeoplastic structure activity relationships of camptothecin and related analogs. In: Chang HM, Yeung HW, Koo A (eds) Advance in Chinese medicinal materials research. World Scientific, singapore, p 391
Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA (1966) Plant antitumor agents: 1. The isolation and structure of camptothecin, a novel alkaloid leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 88: 3888
Wall ME, Wani MC, Natschke SM, Nicholas AW (1986) Plant antitumor agents: 22. Isolation of 11-hydroxycamptothecin from Camptotheca acuminata decne: Total synthesis and biological activity. J Med Chem 29: 1553
Wani MC, Ronman PE, Lindley JT, Wall ME (1980) Plant antitumor agents: 18. Synthesis and biological activity of camptothecin analogues. J Med Chem 23: 554
Wani MC, Nicholas AW, Wall ME (1986) Plant antitumor agents: 23. Synthesis and antileukemic activity of camptothecin analogues. J Med Chem 29: 2358
Xu B, Yang JL (1985) Hydroxycamptothecin as an antitumor agent. In: Chang HM, Yeung HW, Koo A (eds) Advance in Chinese medicinal materials research. World Scientific, Singapore, p 377
Yokokura T, Sawada S, Nokata K, Miyasaka T, Mutai M (1981) Antileukemic activity of new camptothecin derivatives. In: Proceedings of the Japanese Cancer Association, 40th annual meeting, Sapporo, Japan, p 228
Yokokura T, Furuta T, Sawada S, Sugino E, Mutai M, Miyasaka T (1984) Antitumor activity of newly synthesized, lactone ring-closed and water-soluble camptothecin derivative in mice. In: Proceedings of the Japanese Cancer Association, 43rd annual meeting, Fukuoka, Japan, p 261
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Matsuzaki, T., Yokokura, T., Mutai, M. et al. Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. Cancer Chemother. Pharmacol. 21, 308–312 (1988). https://doi.org/10.1007/BF00264196
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00264196