Abstract
Fluorescence-microscopic studies with dansylated estramustine (DnsEM) has permitted investigation of the mechanism of estramustine (EM) uptake in live human prostatic tumor cells (DU 145). DnsEM appeared to enter cells rapidly at the peripheral cell margins. A progressive increase in fluorescence was observed until the perinuclear material and cytoplasm were labeled brightly and the nucleoplasm was labeled faintly. Light microscopy showed that DnsEM is assimilated first in preexisting vesicles and then in numerous newly created vesicles that accumulate in the cytoplasm and around the nucleus. Colony-forming assays showed EM and DnsEM to be equally cytotoxic to cultured DU 145 cells. Cellular uptake and subsequent manifestation of cytotoxicity are presumably dependent upon these vesicles. However, after uptake of DnsEM, its diffusion into the cytoplasm was observed.
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- Aumüller G., Seitz J., Heyns W., Flickinger C. J. Intracellular localization of Prostatic Binding Protein (PBP) in rat prostate by light and electron microscopic immunocytochemistry. Histochemistry. 1982;76(4):497–516. doi: 10.1007/BF00489905. [DOI] [PubMed] [Google Scholar]
- Björk P., Forsgren B., Gustafsson J. A., Pousette A., Högberg B. Partial characterization and "quantitation" of a human prostatic estramustine-binding protein. Cancer Res. 1982 May;42(5):1935–1942. [PubMed] [Google Scholar]
- Hartley-Asp B., Gunnarsson P. O. Growth and cell survival following treatment with estramustine nor-nitrogen mustard, estradiol and testosterone of a human prostatic cancer cell line (DU 145). J Urol. 1982 Apr;127(4):818–822. doi: 10.1016/s0022-5347(17)54057-4. [DOI] [PubMed] [Google Scholar]
- Kanje M., Deinum J., Wallin M., Ekström P., Edström A., Hartley-Asp B. Effect of estramustine phosphate on the assembly of isolated bovine brain microtubules and fast axonal transport in the frog sciatic nerve. Cancer Res. 1985 May;45(5):2234–2239. [PubMed] [Google Scholar]
- Madajewicz S., Catane R., Mittelman A., Wajsman Z., Murphy G. P. Chemotherapy of advanced, hormonally resistant prostatic carcinoma. Oncology. 1980;37(1):53–56. doi: 10.1159/000225402. [DOI] [PubMed] [Google Scholar]
- Stearns M. E. High voltage electron microscopy studies of axoplasmic transport in neurons: a possible regulatory role for divalent cations. J Cell Biol. 1982 Mar;92(3):765–776. doi: 10.1083/jcb.92.3.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stearns M. E., Tew K. D. Antimicrotubule effects of estramustine, an antiprostatic tumor drug. Cancer Res. 1985 Aug;45(8):3891–3897. [PubMed] [Google Scholar]
- Tew K. D., Erickson L. C., White G., Wang A. L., Schein P. S., Hartley-Asp B. Cytotoxicity of estramustine, a steroid-nitrogen mustard derivative, through non-DNA targets. Mol Pharmacol. 1983 Sep;24(2):324–328. [PubMed] [Google Scholar]
- Tew K. D., Hartley-Asp B. Cytotoxic properties of estramustine unrelated to alkylating and steroid constituents. Urology. 1984 Jun;23(6 Suppl):28–33. doi: 10.1016/s0090-4295(84)80094-1. [DOI] [PubMed] [Google Scholar]
- Tew K. D. The mechanism of action of estramustine. Semin Oncol. 1983 Sep;10(3 Suppl 3):21–26. [PubMed] [Google Scholar]
- Wallin M., Deinum J., Fridén B. Interaction of estramustine phosphate with microtubule-associated proteins. FEBS Lett. 1985 Jan 7;179(2):289–293. doi: 10.1016/0014-5793(85)80536-6. [DOI] [PubMed] [Google Scholar]
- Woods K. R., Wang K. T. Separation of dansyl-amino acids by polyamide layer chromatography. Biochim Biophys Acta. 1967 Feb 21;133(2):369–370. doi: 10.1016/0005-2795(67)90078-5. [DOI] [PubMed] [Google Scholar]