Antibiotic heliomycin and its water-soluble 4-aminomethylated derivative provoke cell death in T24 bladder cancer cells by targeting sirtuin 1 (SIRT1).
Year: 2022
Type: article
Abstract: -butylamino)methyl derivative (HD2) directly engaged with SIRT1 in the native cellular environment, whereas another derivative (HD3) did not. Upon binding, heliomycin downregulated SIRT1 protein expression without altering its transcript level, and subsequently induced autophagy. Interestingly, the derivative (HD2) triggered apoptosis. The interaction between SIRT1 protein and heliomycin or its derivatives was also speculated by a molecular docking simulation, suggesting heliomycin (H1) and derivative (HD2) acting with the different binding modes to SIRT1. Given the increased water-solubility, hydrogen bonds were found on Ala262 and Ile347 residues in the docked complex of derivative (HD2) to produce more steady interaction and initiate signaling pathways that were not observed in the case of heliomycin. Meanwhile, it is evident that derivative (HD3) did not engage with SIRT1 by CETSA or molecular docking studies, nor did it downregulate SIRT1 expression. Taken together, these findings clearly show that SIRT1 is targeted and downregulated by heliomycin and its water-soluble 4-aminomethylated derivative (HD2) possibly through autophagic and/or proteasomal degradation, leading to cell death and growth suppression of T24 bladder cancer cells.
Source: PubMed
Authors: Ming Hung Lin, Atikul Islam, Yen-Hui Liu, Chia-Wei Weng, Jun-Han Zhan, Ru-Hao Liang, Alexander S Tikhomirov, Andrey E Shchekotikhin, Pin Ju Chueh
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4225907610