Synthesis, Characterization, and Cytotoxicity of a Series of Estrogen-Tethered Platinum(IV) Complexes
Copyright policy )Synthesis, Characterization, and Cytotoxicity of a Series of Estrogen-Tethered Platinum(IV) Complexes
Several estrogen-tethered platinum(IV) complexes were prepared and characterized by ESI-MS and (1)H NMR spectroscopy. Their design was inspired by the observation that estrogen receptor-positive cells exposed to the hormone are sensitized to cisplatin. Intracellular reduction of bis-estrogen-cis-diamminedichloroplatinum(IV), BEP(n) (where n = 1-5 methylene groups between Pt and estrogen), occurs to afford cisplatin and two equivalents of the linker-modified estrogen. The ability of BEP(n) to induce overexpression of HMGB1 was established by immunofluorescence microscopy. The cytotoxicity of the compounds was evaluated in ER(+) MCF-7 and ER(-) HCC-1937 human breast cancer cell lines. BEP3 selectively induces overexpression of HMGB1 in MCF-7 cells, compared to HCC-1937 cells, and enhances their sensitivity (IC(50) = 2.1 +/- 0.4 microM versus 3.7 +/- 0.9 microM, respectively) to the compound. The difference in compound activities and the potential of compounds of this class for treating breast and ovarian cancer are discussed.
- Massachusetts Institute of Technology United States
- Helio Research United States
- MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Pharmacology, Dose-Response Relationship, Drug, Estradiol, Organoplatinum Compounds, Cell Survival, Clinical Biochemistry, Gene Expression, Breast Neoplasms, Estrogens, Biochemistry, Structure-Activity Relationship, Receptors, Estrogen, Cell Line, Tumor, Drug Design, Drug Discovery, Molecular Medicine, Humans, Drug Screening Assays, Antitumor, HMGB1 Protein, Molecular Biology
Pharmacology, Dose-Response Relationship, Drug, Estradiol, Organoplatinum Compounds, Cell Survival, Clinical Biochemistry, Gene Expression, Breast Neoplasms, Estrogens, Biochemistry, Structure-Activity Relationship, Receptors, Estrogen, Cell Line, Tumor, Drug Design, Drug Discovery, Molecular Medicine, Humans, Drug Screening Assays, Antitumor, HMGB1 Protein, Molecular Biology
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).253 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!