RNAm expression profile of cancer marker genes in HepG2 cells treated with different concentrations of a new indolin-3-one from Pseudomonas aeruginosa

用不同浓度的铜绿假单胞菌新吲哚-3-酮处理 HepG2 细胞后癌症标志物基因的 RNAm 表达谱

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作者:Lucas Milanez Benicio, Ane Stefano Simionato, Cláudio Roberto Novello, Jeconias Rocha Guimarães, Ingrid Felicidade, Admilton Gonçalves de Oliveira, João Carlos Palazzo de Mello, Mário Sérgio Mantovani, Andreas Lazaros Chryssafidis, Galdino Andrade, Ilce Mara de Syllos Colus, Marcelo Tempesta de Oliv

Abstract

The present study tested the effects of a newly identified indolin-3-one compound (compound 1), produced by Pseudomonas aeruginosa, on HepG2 cells. The MTT assays demonstrated decreased metabolic activities in HepG2 cells treated with compound 1, with dose- and time-dependent intensifying effect, starting at a concentration of 40 µM. The IC50 after 24, 48, 72, and 96 h treatments were 41.35, 52.7, 92.79 and 66.65 μM of compound 1, respectively. Below 80 µM, no significative damage on erythrocytes membranes was observed by the hemolytic assays. The RT-qPCR revealed that the compound modulated key genes involved in carcinogenesis process, indicating possible indolin-3-one mechanisms of action. The data showed that gene expression alterations promoted by compound 1, in concentrations up to 60 μM after 48 h, led to a decrease in cellular progression and there was no direct cellular damage. In addition, non-cytotoxic concentrations of compound 1 halved the concentration of the chemotherapeutic doxorubicin, maintaining similar therapeutic effect against HepG2 cells. The novelty of the molecule and the biological activities observed in the present study emphasize the potential of the compound 1 in cancer therapy research.

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