AI Article Synopsis
- MKT-077, a rhodacyanine dye, causes cancer-specific cell death but faces use limitations after clinical trials.
- Researchers introduced YM-1, a more toxic derivative that effectively targets various cancer cell lines while sparing normal cells.
- YM-1 enhances tamoxifen sensitivity in resistant cancer models, possibly by altering estrogen receptor phosphorylation through reduced Akt levels, indicating potential for better treatment strategies.
Article Abstract
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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338522 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035566 | PLOS |
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Article Synopsis
- MKT-077, a rhodacyanine dye, causes cancer-specific cell death but faces use limitations after clinical trials.
- Researchers introduced YM-1, a more toxic derivative that effectively targets various cancer cell lines while sparing normal cells.
- YM-1 enhances tamoxifen sensitivity in resistant cancer models, possibly by altering estrogen receptor phosphorylation through reduced Akt levels, indicating potential for better treatment strategies.
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