title: Antiproliferative effect and apoptotic activity of linear geranylphenol derivatives from phloroglucinol and orcinol.
abstract: Sixteen synthetic linear derivatives geranylphenols, were obtained from phloroglucinol and orcinol, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, PC-3, MDA-MB231, DU-145) and one non-tumor cell line, human dermal fibroblast (HDF). IC50 values were determined at concentrations of 0-100 μM of each compound for 72 h. Compounds 12, 13, 17, 21, 22 and 25, showed cytotoxic activity. To elucidate whether these compounds reduce cell viability by inducing apoptosis, cell lines MCF-7, PC-3 and DHF were treated with each active compound 12, 13, 17, 21, 22 and 25 and were examined after Hoechst 33342 staining. The compounds 12, 13 and 17 induced apoptosis in various cancer cell lines, as shown by nuclear condensation and/or fragmentation. In addition, it was found that compounds 12 and 13, induced changes in mitochondrial membrane permeability in those cancer cell lines. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases inducing the cell death process.
authors.affiliation: Departamento de Química, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso, 2390123, Chile. Electronic address: lautaro.taborga@usm.cl.
authors.forename: Lautaro
authors.initials: L
authors.lastname: Taborga
authors.affiliation: Departamento de Química, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso, 2390123, Chile. Electronic address: luis.espinozac@usm.cl.
authors.forename: Luis
authors.initials: L
authors.lastname: Espinoza
authors.affiliation: Centro Investigaciones Biomédicas (CIB), Facultad de Medicina, Universidad de Valparaíso, Hontaneda 2653, Valparaíso, 2341386, Chile. Electronic address: alejandra.moller@uv.cl.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Moller
authors.affiliation: Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Llano Subercaseaux 2801, San Miguel, Santiago, 8900000, Chile. Electronic address: hector.carrasco@uautonoma.cl.
authors.forename: Héctor
authors.initials: H
authors.lastname: Carrasco
authors.affiliation: Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña 1093, Playa Ancha, Valparaíso, 2360102, Chile. Electronic address: mauricio.cuellar@uv.cl.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cuellar
authors.affiliation: Centro Investigaciones Biomédicas (CIB), Facultad de Medicina, Universidad de Valparaíso, Hontaneda 2653, Valparaíso, 2341386, Chile. Electronic address: juan.villena@uv.cl.
authors.forename: Joan
authors.initials: J
authors.lastname: Villena
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012118:Resorcinols / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012118:Resorcinols; C005282:orcinol; D010696:Phloroglucinol
keywords: Apoptosis; Cancer cell lines; Caspase-3 activity; Cytotoxic activity; Linear geranylphenols; Mitochondrial membrane permeability