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- W4293203707 startingPage "114691" @default.
- W4293203707 abstract "Platinum(IV) prodrugs c,c,t-[PtCl2(NH3)2(OH)(amlexanox)] (MAP) and c,c,t-[PtCl2(NH3)2(amlexanox)2] (DAP) were synthesized by reacting amlexanox with oxoplatin and characterized by NMR, HR-MS, HPLC, and elemental analysis. The complexes could be reduced to platinum(II) species and amlexanox to exert antitumor activity. Generally, MAP was more potent than DAP and cisplatin towards various human cancer cell lines; particularly, it was active in cisplatin-resistant Caov-3 ovarian cancer and A549/DDP lung cancer cells. MAP induced serious damage to DNA, remarkable change in mitochondrial morphology, decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria, and up-regulation of pro-apoptotic protein Bax in Caov-3 cells, thereby leading to evident apoptosis. Meanwhile, MAP markedly promoted the autophagic flux, including affecting the expression of microtubule-associated protein light chain 3 (LC3) and autophagy adaptor protein p62 in Caov-3 cells, with an increase in the ratio of LC3-II/LC3-I and a decrease in p62, thus trigging the occurrence of autophagy. The MAP-induced bimodal cell death mode is uncommon for platinum complexes, which presents a new possibility to invent anticancer drugs with unique mechanism of action." @default.
- W4293203707 created "2022-08-27" @default.
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- W4293203707 date "2022-11-01" @default.
- W4293203707 modified "2023-10-09" @default.
- W4293203707 title "Amlexanox-modified platinum(IV) complex triggers apoptotic and autophagic bimodal death of cancer cells" @default.
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- W4293203707 doi "https://doi.org/10.1016/j.ejmech.2022.114691" @default.
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