PloS one, 2012-04, Vol.7 (4), p.e35566
2012
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- Autor(en) / Beteiligte
- Titel
- Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance
- Ist Teil von
- PloS one, 2012-04, Vol.7 (4), p.e35566
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0035566Titel-ID: cdi_plos_journals_1324590254
- Format
- –
- Schlagworte
- AKT protein, Analysis, Biology, Biotechnology, Breast cancer, Cancer, Cancer therapies, Cell culture, Cell death, Cell Line, Tumor, Cell Survival - drug effects, Chemistry, Clinical trials, Complications, Cytotoxicity, Departments, Doxorubicin - analogs & derivatives, Doxorubicin - chemistry, Doxorubicin - toxicity, Drug Resistance, Neoplasm - drug effects, Estrogen Receptor alpha - metabolism, Estrogens, Heat shock proteins, HEK293 Cells, HeLa Cells, Humans, Kinases, Life sciences, Medical research, Medicine, Mutation, Neoplasms - metabolism, Neoplasms - pathology, Pathology, Pharmacology, Phosphorylation, Proto-Oncogene Proteins c-akt - metabolism, Pyridinium Compounds - chemistry, Pyridinium Compounds - toxicity, Sensitivity, Tamoxifen, Tamoxifen - pharmacology, Thiazoles - chemistry, Thiazoles - toxicity, Toxicity, Tumor cell lines