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Effects of N-trifluoroacetyladriamycin-14-valerate (AD-32) on human bladder tumor cell lines

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  • N-trifluoroacetyl-adriamycin-14-valerate
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Summary

We have compared the in vitro activity of N-trifluoroacetyladriamycin-14-valerate (AD-32) and doxorubicin hydrochloride (ADR) on the clonal growth of human bladder tumor cell lines (HBTCL). In order to determine the relative toxicity of ADR and AD-32 on hematopoietic stem cells, CFU-GM assays were set up using 10 normal human bone marrow samples. The mean lethal dose for 50% of the colonies (LD-50) for ADR was 1.6±1.4 μM and that for AD-32, 3.9±4.9 μM (P<0.55),suggesting that these agents have similar bone marrow toxicity. Both drugs produced enhanced inhibition of clonal growth of HBTCL with increasing C × Ts. The spectrum of activity of the two drugs was similar against a panel of seven HBTCL. The activity of ADR was inhibited at 4 °C while the activity of AD-32 was unaffected by temperature. ADR was more effective against HBTCL in the log growth phase than the plateau phase while the reverse was found using AD-32. Verapamil was found to enhance the activity of both ADR and AD-32 against a HBTCL (T24), found to be resistant to both agents. The lipophilic properties of AD-32, along with its enhanced activity when used over prolonged periods of time and its activity against tumor cells in the plateau phase, suggest that AD-32 could be useful in the management of patients with superficial bladder cancer.

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Abbreviations

ADR:

doxorubicin hydrochloride

AD-32:

N-trifluoroacetyladriamycin-14-valerate

HBTCL:

human bladder tumor cell lines

CFU-GM:

corony forming units-granulocyte, macrophage

CFU-T:

colony-forming units-tumor

C × T:

concentration × time of drug exposure

HBSS:

Hank's balanced salt solution

FCS:

fetal calf serum

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Authors and Affiliations

  1. Research Service, V. A. Medical Center, Memphis, and the Department of Internal Medicine, Pediatrics, Pharmacology and Medicinal Chemistry, University of Tennessee-Memphis, 38163, TN, USA

    Harvey B. Niell, Robert F. Hunter, Henry G. Herrod & Mervyn Israel

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  1. Harvey B. Niell
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  2. Robert F. Hunter
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  3. Henry G. Herrod
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  4. Mervyn Israel
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Niell, H.B., Hunter, R.F., Herrod, H.G. et al. Effects of N-trifluoroacetyladriamycin-14-valerate (AD-32) on human bladder tumor cell lines. Cancer Chemother. Pharmacol. 19, 47–52 (1987). https://doi.org/10.1007/BF00296255

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  • DOI: https://doi.org/10.1007/BF00296255

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