title: Antiproliferative effect of benzophenones and their influence on cathepsin activity.
abstract: The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantification of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7-epiclusianone showed a dose-dependent cytotoxic effect. The IC(50) values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition.
authors: Department of Physiological Sciences, Faculty of Dentistry of Piracicaba, State University of Campinas (UNICAMP), SP, Brazil. ramiro@fop.unicamp.br
authors: Ramiro Mendonça
authors: RM
authors: Murata
authors: Regiane
authors: R
authors: Yatsuda
authors: Marcelo Henrique
authors: MH
authors: dos Santos
authors: Luciana K
authors: LK
authors: Kohn
authors: Felipe Terra
authors: FT
authors: Martins
authors: Tanus Jorge
authors: TJ
authors: Nagem
authors: Severino Matias
authors: SM
authors: Alencar
authors: João Ernesto
authors: JE
authors: de Carvalho
authors: Pedro Luiz
authors: PL
authors: Rosalen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001577:Benzophenones / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D028084:Clusiaceae / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: C118110:7-epiclusianone; D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C528023:garciniaphenone; D002403:Cathepsins