Summary
Anguidine pretreatment was previously shown to potentiate cis-platinum in Chinese hamster ovary cells by 100-fold, probably by enhancing cellular cis-platinum. uptake. Since both cis-platinum and anguidine have been reported to have clinical efficacy in human brain tumors, the present study was initiated to investigate whether anguidine's potentiation of cis-platinum was applicable to human brain tumor cells in culture. Using the colony formation assay, it was found that anguidine enhanced cis-platinum's cytotoxicity by ten-fold, producing a dose modification factor of 1.74. Alkaline elution analysis of cis-platinum-induced DNA crosslinks found that anguidine enhanced cross-linking by a factor of 1.55, 1.76, 1.63, and 1.48 at 0, 6, 24, and 48 hr, respectively, after cis-platinum treatment. This enhancement of cross-linking is evidence for anguidine increasing cis-platinum uptake. Thus, anguidine enhances cis-platinum-induced DNA cross-linking and subsequent cytotoxicity in human brain tumor cells, and may be clinically useful in combination with cis-platinum in those tumors.
Similar content being viewed by others
References
Edwards MS, Levin VA, Wilson CB: Brain tumor chemotherapy: An evaluation of agents in current use for phase II and III trials. Cancer Treat Rep 64:1179–1205, 1980.
Jelsma R, Bucy PL: The treatment of glioblastoma multiforme of the brain. J Neurosurg 27:388–400, 1967.
Walker MD, Green SB, Byar DP et al: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. The New Engl Jour Med 23:1323–1329, 1980.
Armentrout SA, Foltz E, Vermund H et al: Comparison of postoperative irradiation alone and in combination with BCNU (NSC-409962) in the management of malignant gliomas. Cancer Chemother Rep 58:841–844, 1974.
Weir B, Band P, Urtasun R et al: Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas. J Neurosurg 45:129–134, 1979.
Khan A, McCullough D, Borts F, Sinks LF: Update on use of cis-platinum in CNS malignancies. Proc Am Assoc Cancer Res 21:390, 1980.
Leventhal BG, Freeman A: Cis-diamminedichloroplatinum — A phase II study in pediatric malignancies. Proc Am Assoc Cancer Res 20:197, 1979.
Rozencweig M, Von Hoff DD, Slavik M, Muggia F: Cisdiamminedichloroplatinum: A new anticancer drug. Ann Intern Med 86:803–812, 1977.
Stewart DS, Leavens M, Maor M, Fenn L, LunaM, Bonura J, Caprioli R, Loo TL, Benjamin R: Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Res 42:2474–2479, 1982.
Vich NA, Khandekar JB, Blaner DD: Chemotherapy of brain tumors. The ‘blood-brain barrier’ is not a factor. Arch Neurol 34:523–526, 1977.
Hromas R, Meyn R, Jenkins S, Barlogie B: Anguidine enhances cis-platinum-induced DNA cross-links in Chinese Hamster Ovary cells. Proc Am Assoc Cancer Res 25:370, 1984.
Hromas RA, Barlogie B, Swartzendruber D, Drewinko B: Potentiation of DNA-reactive antineoplastic agents and protection against S-phase-specific agents by anguidine in Chinese hamster ovary cells. Cancer Res 43:3070–3073, 1983.
Murphy WK, Burgess MS, Valdevieso M, Livingston RB, Bodey GP, Freireich EJ: Phase I clinical evaluation of anguidine. Cancer Treat Rep 62:1497–1502, 1978.
Yap MY, Murphy WK, Distefano A, Blumenschein GR, Bodey GP: Phase II study of anguidine in advanced breast cancer. Cancer Treat Rep 63:789–791, 1979.
Thigpen JT, Vaughn C, Stuckey WJ: Phase II trial of anguidine in patients with sarcomas unresponsive to prior chemotherapy: A Southwest Oncology Group study. Cancer Treat Rep 65:881–882, 1981.
Goodwin W, Stephens R, McCracken JD, Groppe C: Therapy for advanced colorectal cancer with a combination of 5-FU and anguidine: A Southwest Oncology Group study. Cancer Treat Rep 65:359, 1981.
Goodwin JW, Bottomley RH, Vaughn CB, Frank J, Pugh RP: Phase II evaluation of anguidine in central nervous system tumors: A Southwest Oncology Group study. Cancer Treat Rep 67:285–286, 1983.
Yung W-KA, Shapiro JR, Shapiro WR: Heterogenous chemosensitivities of subpopulations of human glioma cells in culture. Cancer Res 42:992–998, 1982.
Puck TT, Marcus PI: A rapid method for viable cell titration and clone production with HeLa cells in tissue culture. Proc Natl Acad Sci USA 41:432–437, 1955.
Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep 50:219–244, 1966.
Kohn KW, Grimek-Ewig RA: Alkaline elution analysis, a new approach to the study of DNA single strand interruption in cells. Cancer Res 33:1849–1853, 1973.
Kohn KW, Erickson LC, Ewig RAG, Friedman LA: Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry 15:4629–4637, 1976.
Kohn KW, Ewig RAG, Erickson LC, Zwelling LA: Measurement of strand breaks and cross-links in DNA by alkaline elution. In: Freidberg E, Hanowalat P (eds) DNA repair: A Laboratory Manual of Research Procedures, Marcel Dekker, New York, 1981, pp 379–401.
Meyn RE, Jenkins SF, Thompson LH: Defective removal of DNA cross-links in a repair-deficient mutant of Chinese hamster cells. Cancer Res 42:3106–3110, 1982.
Erickson LC, Zwelling LA, Ducore JM, Sharkey NA, Khon KW: Differential cytotoxicity and DNA cross-linking in normal and transformed human fibroblasts treated with cisdiamminedichloroplatinum II. Cancer Res 41:2791–2794, 1984.
Ducore JM, Erickson LC, Zwelling LA, Laurent G, Kohn KW: Comparative studies of DNA cross-linking and cytotoxicity in Burkitt's lymphoma cell lines treated with cis-diamminedichloroplatinum II and L-phenylalanine mustard. Cancer Res 42:897–902, 1982.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hromas, R.A., Yung, W.A. Anguidine potentiates cis-platinum in human brain tumor cells. J Neuro-Oncol 3, 343–348 (1986). https://doi.org/10.1007/BF00165584
Issue Date:
DOI: https://doi.org/10.1007/BF00165584