Cytotoxic effects induced by combination of heliantriol B2 and dequalinium against human leukemic cell lines

VELA GUROVIC, MARÍA SOLEDAD; DIAZ LANZA, ANA M.; BOYANO ADANEZ, M; ESTAÑ OMAÑA, M; GAÑAN GOMEZ, I; ANA PAULA MURRAY; SANCHO LOPEZ, PILAR

PHYTOTHERAPY RESEARCH

JOHN WILEY & SONS LTD

Año: 2011 vol. 25 p. 603 - 610

0951-418X

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 IC50 values of 1.98 ± 0.12 microM and 3.52 ± 0.14 microM 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 analyzed by Annexin V/PI labeling. Mitochondrial alterations including reactive oxygen species (ROS) production and mitochondrial transmembrane potential (deltaØm) were also tested. The results demonstrated that HB2 induces cell death by apoptosis and necrosis and shows enhanced cytotoxic effects in combination with DQA. Besides, HB2 induces ROS overproduction on NB4 cells and a slight decrease of deltaØm. Consequently, our findings prompt further studies on HB2 mechanism of action and its selectivity to tumor cells in order to assess the potential of HB2 as an agent for cancer treatment.