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- W2968853373 abstract "Platinum drugs including cisplatin are widely used in clinics to treat various types of cancer. However, the lack of cancer-cell selectivity is one of the major problems that lead to side effects in normal tissues. Luteinizing hormone-releasing hormone (LHRH) receptors are overexpressed in many types of cancer cells but rarely presented in normal cells, making LHRH receptor a good candidate for cancer targeting. In this study, we report the synthesis and cytotoxic study of a novel platinum(IV) anticancer prodrug functionalized with LHRH peptide. This LHRH-platinum(IV) conjugate is highly soluble in water and quite stable in a PBS buffer. Cytotoxic study reveals that the prodrug selectively targets LHRH receptor-positive cancer cell lines with the cytotoxicities 5-8 times higher than those in LHRH receptor-negative cell lines. In addition, the introduction of LHRH peptide enhances the cellular accumulation in a manner of receptor-mediated endocytosis. Moreover, the LHRH-platinum(IV) prodrug is proved to kill cancer cells by binding to the genomic DNA, inducing apoptosis, and arresting the cell cycle at the G2/M phase. In summary, we report a novel LHRH-platinum(IV) anticancer prodrug having largely improved selectivity toward LHRH receptor-positive cancer cells, relative to cisplatin." @default.
- W2968853373 created "2019-08-22" @default.
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- W2968853373 date "2019-08-08" @default.
- W2968853373 modified "2023-09-26" @default.
- W2968853373 title "Synthesis and Cytotoxic Study of a Platinum(IV) Anticancer Prodrug with Selectivity toward Luteinizing Hormone-Releasing Hormone (LHRH) Receptor-Positive Cancer Cells" @default.
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- W2968853373 doi "https://doi.org/10.1021/acs.inorgchem.9b01583" @default.
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