title: Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity.
abstract: Phenolic compounds are known for their cytotoxic properties against cancer cells despite their still unclear general mechanism of action. Herein is reported the evaluation of the cytotoxic effects of on human osteosarcoma cells of nine phenol derivatives against osteosarcoma cells, and some insights on their mechanism.
  
  
  
  The cytotoxicity was characterized by cell viability, scratch assay, cellular DNA content measurement, Annexin V apoptosis, mitochondrial calcium and caspase 3/7 assays. The study shows that out of the nine compounds used in this study, a tetrahydroquinoline derivative, 2-((1,2,3,4-tetrahydroquinolin-1-yl)(4- methoxyphenyl)methyl) phenol, was found to exhibit strong inhibitory response with IC50 of 50.5 ± 3.8 µM, and therefore can be a potential chemotherapeutic agent. Further experiments revealed that this compound induces cell death by apoptosis and also act as a migration inhibitor. Analysis of the mitochondrial calcium following treatment with the compound on U2OS cells showed a significant reduction in the level of mitochondrial calcium concentration suggesting a mitochondrial calcium-independent mechanism in triggering apoptosis. Treatment of HEK293 cells with the compound confirmed the cytotoxic effects of the compound, however, an increase in the level of mitochondrial calcium was observed. Moreover, the caspase 3/7 mediated cell death was also observed in both cell types.
  
  
  
  Overall, the study suggests that the derivatives of this compound can be used for development of new therapeutics for osteosarcoma and other cancers.
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Anzhelika
authors.initials: A
authors.lastname: Karjalainen
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Phuong
authors.initials: P
authors.lastname: Doan
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Jerome G
authors.initials: JG
authors.lastname: Chandraseelan
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Ossi
authors.initials: O
authors.lastname: Sandberg
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.affiliation: Dept of Chemistry and Bioengineering, Tampere University of Technology, Korkeakoulunkatu 8, 33101 Tampere. Finland.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: Candeias
authors.affiliation: Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
authors.forename: Meenakshisundaram
authors.initials: M
authors.lastname: Kandhavelu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D010636:Phenols; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D002118:Calcium
keywords: Phenol-derivatives; anticancer; biological screening; cell death; cytotoxicity; mitochondria