title: Cytotoxic effects induced by combination of heliantriol B2 and dequalinium against human leukemic cell lines.
abstract: Natural occurring compounds are considered an important source of antitumoral agents. In the present study, the cytotoxic potential of three pentacyclic triterpenes isolated from Chuquiraga erinacea (Asteraceae), against the human leukemic cell lines NB4 and K562 was assessed. Heliantriol B2 (HB2) showed the highest cytotoxic activity after 24 h treatment showing IC(50) values of 1.98 ± 0.12 µm and 3.52 ± 0.14 µm for NB4 and K562 cells, respectively. This activity was higher than that of the reference compound dequalinium (DQA). Apoptosis and necrosis induced by HB2 in both NB4 and K562 cell lines were analysed by Annexin V/PI labeling. Mitochondrial alterations including reactive oxygen species (ROS) production and mitochondrial transmembrane potential (ΔΨm) were also tested. The results demonstrated that HB2 induced cell death by apoptosis and necrosis and showed enhanced cytotoxic effects in combination with DQA. Besides, HB2 induced ROS overproduction in NB4 cells and a slight decrease of ΔΨm. Consequently, our findings prompt further studies on the HB2 mechanism of action and its selectivity to tumor cells in order to assess the potential of HB2 as an agent for cancer treatment.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain. svela@uns.edu.ar
authors.forename: M Soledad Vela
authors.initials: MS
authors.lastname: Gurovic
authors.forename: A María Díaz
authors.initials: AM
authors.lastname: Lanza
authors.forename: María del Carmen Boyano
authors.initials: Mdel C
authors.lastname: Adánez
authors.forename: M Cristina Estañ
authors.initials: MC
authors.lastname: Omaña
authors.forename: Irene Gañán
authors.initials: IG
authors.lastname: Gómez
authors.forename: A Paula
authors.initials: AP
authors.lastname: Murray
authors.forename: Pilar Sancho
authors.initials: PS
authors.lastname: López
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003868:Dequalinium / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D009336:Necrosis; D053978:Pentacyclic Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; C559101:heliantriol B2; D003868:Dequalinium