MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells.

Related Articles

MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells.

Invest New Drugs. 2018 Dec 19;:

Authors: Maioral MF, Stefanes NM, Bigolin Á, Zatelli GA, Philippus AC, de Barcellos Falkenberg M, Santos-Silva MC

Abstract
Plants are important sources of biologically active compounds and they provide unlimited opportunities for the discovery and development of new drug leads, including new chemotherapeutics. Miconidin acetate (MA) is a hydroquinone derivative isolated from E. hiemalis. In this study we demonstrated that MA was cytotoxic against acute leukemia (AL), solid tumor cells and cancer stem cells, with the strongest effect exhibited against AL. Furthermore, it was non-cytotoxic against non-tumor cells and did not cause significant hemolysis. MA blocks the G2/M phase and causes cytostatic effects, acting in a similar way to dexamethasone by increasing PML expression. The compound also triggered intrinsic and extrinsic apoptosis by modulating Bax, FasR and survivin expression. This led to an extensive mitochondrial damage that resulted in AIF, cytochrome c and endonuclease G release, caspase-3 and PARP cleavage and DNA fragmentation. We have further demonstrated that MA was strongly cytotoxic against neoplastic cells collected from patients with different AL subtypes. Interestingly, MA increased the cytotoxic effect of chemotherapeutics cytarabine and vincristine. This study indicates that MA may be a new agent for AL and highlights its potential as a new source of anticancer drugs. Graphical abstract MA blocks G2/M phase with PML expression and KI67 inhibition, ROS generation and intrinsic and extrinsic apoptosis, leading to mitochondrial damage, caspase 3 and PARP cleavage and DNA fragmentation.

PMID: 30569243 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2BuHjxc