Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines

Toxicol In Vitro. 2016 Aug:34:237-245. doi: 10.1016/j.tiv.2016.04.007. Epub 2016 Apr 11.

Abstract

Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma.

Keywords: Biflorin; Cell cycle progression; Human melanoma; Repair genes; Replication genes; SK-Mel.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA / metabolism*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • GTP Phosphohydrolases / genetics
  • Humans
  • Melanoma / genetics*
  • Membrane Proteins / genetics
  • Mutation
  • Naphthoquinones / toxicity*
  • Protein Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Thymidylate Synthase / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / genetics
  • ras Proteins / genetics

Substances

  • Membrane Proteins
  • Naphthoquinones
  • RRAD protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • biflorin
  • DNA
  • DNA Modification Methylases
  • TYMS protein, human
  • Thymidylate Synthase
  • MGMT protein, human
  • MELK protein, human
  • BRAF protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • ras Proteins
  • DNA Repair Enzymes