Abstract | PURPOSE:
Cisplatin (DDP) is an effective antitumor agent limited in its efficacy by the development of tumor cell resistance. The defective accumulation of DDP has been shown to be a prominent feature in many DDP-resistant cell lines. In an effort to circumvent this problem, we examined the cellular accumulation of DDP in the presence of terbium (Tb3+). We also examined the effects of verapamil on the cellular accumulation of DDP in order to delineate the specific interaction of Tb3+ and DDP. All experiments were performed on DDP-sensitive or DDP-resistant MDA-MB-231 human breast tumor cells. METHODS: The cellular accumulation of DDP and verapamil were determined by electrothermal atomic absorption spectrophotometry. Time-resolved luminescence spectroscopy was used to obtain equilibrium binding constants for the Tb3+/MDA cell complexes. RESULTS: We found that 100 microM Tb3+ increased DDP accumulation in the parent MDA cell line, 5.7-fold resistant MDA/A13 and 10-fold resistant MDA/CH cells by 56.2 +/- 7.4, 71.9 +/- 9.4 and 50.8 +/- 9.4%, respectively (P < 0.0001 for all MDA cell types). In contrast, 20 microM verapamil had no significant effect on DDP accumulation in the MDA cell lines. In addition, a positive correlation between the membrane binding of Tb3+ and the cellular accumulation of DDP was found to exist in the parent cell line and sublines (r = 0.9). CONCLUSIONS: In agreement with earlier studies, the plasma membrane of MDA cell lines contain a specific Tb(3+)- binding protein. Our findings suggest that the Tb(3+)- binding protein may be intimately associated with the accumulation of DDP in breast tumor cells.
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Authors | K M Mack, R G Canada, P A Andrews |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 39
Issue 3
Pg. 217-22
( 1997)
ISSN: 0344-5704 [Print] Germany |
PMID | 8996523
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Calcium Channel Blockers
- Terbium
- Verapamil
- Cisplatin
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Topics |
- Analysis of Variance
- Antineoplastic Agents
(metabolism)
- Breast Neoplasms
(metabolism)
- Calcium Channel Blockers
(pharmacology)
- Cisplatin
(metabolism)
- Drug Resistance, Neoplasm
- Female
- Humans
- Middle Aged
- Terbium
(metabolism, pharmacology)
- Tumor Cells, Cultured
(metabolism)
- Verapamil
(pharmacology)
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