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

• Published in: Cancer chemotherapy and pharmacology Vol. 19; no. 1; pp. 47 - 52
• Main Authors: NIELL, H. B, HUNTER, R. F, HERROD, H. G, ISRAEL, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-01-1987
• Subjects: Antineoplastic agents; Biological and medical sciences; Biological Transport; Cell Line; Doxorubicin - analogs & derivatives; Doxorubicin - metabolism; Doxorubicin - pharmacology; Doxorubicin - toxicity; Drug Evaluation, Preclinical; Drug Resistance; Drug Synergism; General aspects; Hematopoietic Stem Cells - drug effects; Humans; Medical sciences; Pharmacology. Drug treatments; Temperature; Tumor Stem Cell Assay; Urinary Bladder Neoplasms - pathology; Verapamil - pharmacology; Antineoplastic agent; Human; Cell line; Urinary bladder; Cytotoxicity; Anthracyclins; In vitro; Tumor cell; Comparative study
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00296255

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 relatively 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 microM and that for AD-32, 3.9 +/- 4.9 microM (P less than 0.55), suggesting that these agents have similar bone marrow toxicity. Both drugs produced enhanced inhibition of clonal growth of HBTCL with increasing C X 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 degrees 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.