title: Chalcone derivatives cause accumulation of colon cancer cells in the G2/M phase and induce apoptosis.
abstract: OBJECTIVE
  Chalcones, naturally occurring open-chain polyphenols abundant in plants, have demonstrated antiproliferative activity in several cancer cell lines. In the present study, the potential anticancer activity of two synthetic analogues named Ch1 and Ch2 in colon cancer cell line was investigated.
  
  
  METHODS
  Antiproliferative activities of both synthetic analogues were assessed by Growth Inhibition Assay (MTT) and xCELLigence cell analysis. Apoptosis was assessed by annexin V/PI staining (early stage) or by DNA fragmentation (final stage). To study the cell death mechanism induced by tested substances, we assessed a series of assays including measurements of the caspase 3 activity, membrane mitochondrial potential (MMP) changes, reactive oxygen species (ROS) production by flow cytometry and expression of important apoptosis-related genes by realtime PCR.
  
  
  RESULTS
  We found concentration and time-dependent cytotoxicity, inhibition of proliferation of Caco-2 cells after Ch1 and Ch2 treatment in parallel with G2/M phase cell cycle arrest and increased cell proportion in subG0/G1 population with annexin V positivity. We demonstrated that both Ch1 and Ch2 induced caspase-dependent cell death associated with increased ROS production, suppressed Bcl-2 and Bcl-xL and enhanced Bax expression. Treatment of Ch1 also suppressed α-, α1- and β5-tubulins, on the other hand Ch2 only suppressed α-tubulin expression.
  
  
  CONCLUSIONS
  Presented chalcones induce apoptosis by intrinsic pathways, and therefore may be an interesting strategy for cancer therapy.
authors.affiliation: P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kello
authors.affiliation: P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic; Institute of Animal Physiology and Genetics AS CR, v.v.i., Libechov, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Drutovic
authors.affiliation: P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic.
authors.forename: Martina Bago
authors.initials: MB
authors.lastname: Pilatova
authors.affiliation: P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic.
authors.forename: Vierka
authors.initials: V
authors.lastname: Tischlerova
authors.affiliation: Institute of Pharmaceutical Chemistry, Faculty of Medicine, University of Pecs, Pecs, Hungary.
authors.forename: Pal
authors.initials: P
authors.lastname: Perjesi
authors.affiliation: P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic. Electronic address: jan.mojzis@upjs.sk.
authors.forename: Jan
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology*; D053938:DNA Fragmentation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014404:Tubulin / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D017382:Reactive Oxygen Species; D014404:Tubulin; D053148:Caspase 3
keywords: Antiproliferative; Apoptosis; Cell cycle arrest; Chalcones; Colorectal cancer