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.
References
Dec 16, 1983·Journal of Immunological Methods·T Mosmann
Jul 4, 2001·Nature Cell Biology·P M Comoglio
Apr 25, 2002·Nucleic Acids Research·Michael W PfafflLeo Dempfle
Jun 19, 2002·The Journal of Biological Chemistry·Alvaro J ObayaJohn M Sedivy
Jun 28, 2002·Cancer Cell·Laura K ShawverAxel Ullrich
Sep 19, 2002·Trends in Pharmacological Sciences·Marie KnockaertLaurent Meijer
Jan 16, 2003·Biomaterials·Dagmar FischerThomas Kissel
May 28, 2003·Cancer Letters·David BernhardAdam Csordas
Jun 20, 2003·Cell Proliferation·Katrien VermeulenZwi N Berneman
May 13, 2004·Toxicology·S KnasmüllerB J Majer
May 13, 2004·Toxicology·Volker Mersch-SundermannFekadu Kassie
Jun 1, 2005·Cancer Letters·James G ChristensenRavi Salgia
Sep 21, 2006·Molecular Cancer Therapeutics·Giuliana CassinelliFranco Zunino
Oct 2, 2007·Oncogene·H WangM A Nikiforov
Apr 18, 2008·Environmental and Molecular Mutagenesis·Irena HreljacMetka Filipic
Sep 25, 2008·Nature Reviews. Molecular Cell Biology·Helfrid HocheggerTim Hunt
Dec 23, 2008·Cancer Letters·Christine M Stellrecht, Varsha Gandhi
Feb 25, 2009·Nucleic Acids Research·J M RuijterA F M Moorman
Jun 16, 2009·Journal of Medicinal Chemistry·Gerald J RothFrank Hilberg
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 2, 2011·International Journal of Pharmaceutics·Regina Scherliess
Jun 28, 2011·British Journal of Pharmacology·A M LathamS Ponnambalam
Oct 25, 2011·European Journal of Medicinal Chemistry·Hongbin ZouYongping Yu
Jan 10, 2012·Electrophoresis·Patrick S ArandaCheryl L Jorcyk
Apr 5, 2012·Critical Reviews in Oncogenesis·Andrew StoneElizabeth A Musgrove
Apr 25, 2012·Annual Review of Analytical Chemistry·Sara A LoveChristy L Haynes
Sep 15, 2012·Methods : a Companion to Methods in Enzymology·Jan M RuijterJo Vandesompele
Apr 9, 2013·Journal of Natural Medicines·Alfarius Eko Nugroho, Hiroshi Morita
Jul 3, 2013·Bioorganic & Medicinal Chemistry·Sara PellegrinoMaria Luisa Gelmi
Sep 4, 2013·Bioorganic & Medicinal Chemistry Letters·Lei DingPing Wei
Jan 31, 2015·Nature Reviews. Drug Discovery·Uzma AsgharErik S Knudsen
Nov 13, 2015·Expert Opinion on Therapeutic Patents·Alberto LeoniMirella Rambaldi
Dec 15, 2015·Scientific Reports·Chunmei GuoMing-Zhong Sun
Oct 5, 2016·Current Topics in Medicinal Chemistry·Dhanya Sunil, Pooja R Kamath
Oct 5, 2016·Recent Patents on Anti-cancer Drug Discovery·Anuj K RathiRahul V Patel
Sep 1, 2017·Scientific Reports·Yajie WangNing Wei