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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(III)‐arene complex, Rh1, that exhibited promising antiproliferative effects in several tumor cell lines. Rh1 induced cell death through the autophagy, cell cycle arrest, and accumulation of intracellular reactive oxygen species (ROS). In addition, Rh1 upregulated the global N6‐methyladenosine (m6A) 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 m6A, highlighting the potential of metal‐based agents to target and regulate epitranscriptomics for tumor suppression.
Chinese Journal of Chemistry – Wiley
Published: May 15, 2022
Keywords: Rhodium; mRNA; Antiproliferation; FTO; m 6 A
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