Metallodrugs with fine-tuned coordination between metals and bioactive ligands can achieve cytotoxic effects in cancer therapy and have been considered as a new approach for drug design.However,it has yet to be elucid...Metallodrugs with fine-tuned coordination between metals and bioactive ligands can achieve cytotoxic effects in cancer therapy and have been considered as a new approach for drug design.However,it has yet to be elucidated whether these metallodrugs target epitranscriptomic proteins for gene expression regulation.This report describes a rhein-based Rh(l)-arene complex,Rh1,that exhibited promising antiproliferative ffects in several tumor cellines.Rh1 induced cell death through the autophagy,cell cycle arrest,and accumulation of intracllular reactive oxygen species(ROs),In addition,Rh1 upregulated the global N^(6)-methyladenosine(m^(6)A)levels in A549 cells in the fat mass-and obesity-associated protein(FTO)-dependent manner.Collectively,the metal-based FTO inhibitor Rh1 effectively suppressed tumor cell proliferation and modulated the abundance of cellular m^(6)A,highlighting the potential of metal-based agents to target and regulate epitranscriptomics for tumor suppression.展开更多
基金We thank NSFC(Nos.22077066,21771109,21778033,21701195,21837006,21977052 and 21907101).
文摘Metallodrugs with fine-tuned coordination between metals and bioactive ligands can achieve cytotoxic effects in cancer therapy and have been considered as a new approach for drug design.However,it has yet to be elucidated whether these metallodrugs target epitranscriptomic proteins for gene expression regulation.This report describes a rhein-based Rh(l)-arene complex,Rh1,that exhibited promising antiproliferative ffects in several tumor cellines.Rh1 induced cell death through the autophagy,cell cycle arrest,and accumulation of intracllular reactive oxygen species(ROs),In addition,Rh1 upregulated the global N^(6)-methyladenosine(m^(6)A)levels in A549 cells in the fat mass-and obesity-associated protein(FTO)-dependent manner.Collectively,the metal-based FTO inhibitor Rh1 effectively suppressed tumor cell proliferation and modulated the abundance of cellular m^(6)A,highlighting the potential of metal-based agents to target and regulate epitranscriptomics for tumor suppression.
