Relationship between cellular accumulation of rhodamine 123 (R123) and cytotoxicity in B16 melanoma cells

David N. Krag, Alain P Theon, Lydia Gan, Jon Wardell, Zhen Tao Shi Zhen Tao

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Rhodamine 123 (R123) is a mitochondria-specific prototype anticancer agent because its target is the energy-producing mechanism of the cell. The goal of this study was to investigate the relationship between intracellular R123 accumulation and cytotoxicity in a R123-sensitive cell line (RS) and a R123-resistant subline (RR) that we developed. Cytotoxicity after exposure to R123 (0-60 μg/ml) was assessed using the clonogenic assay. Intracellular R123 was extracted with acid-alcohol and measured by fluorimetry. The rate of R123 accumulation over 1 hr was significantly higher (P < 0.0001) for RS cells (4.65 ± 0.39 μg/min/106 cells) than for RR cells (1.29 ± 0.24 μg/min/106 cells). R123 accumulation in RS cells was strongly correlated (r = 0.80; P < 0.0001) with cytotoxicity. Treatment of RR cells with verapamil (100 μM) reversed R123 resistance. The resulting dose-survival curve was identical to the dose-response curve of RS cells treated with R123 alone. Cellular content of R123 in RR cells treated with verapamil increased to a level similar to that of RS cells and correlated with cytotoxicity. These data suggest that cytotoxicity of R123 in B16 cells results from increased cellular accumulation of R123.

Original languageEnglish (US)
Pages (from-to)361-365
Number of pages5
JournalJournal of Surgical Research
Volume46
Issue number4
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Surgery

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