An apolar extract of Critonia morifolia inhibits c-Myc, cyclin D1, Cdc25A, Cdc25B, Cdc25C and Akt and induces apoptosis
Affiliations: Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria, Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, 783 71 Olomouc, Czech Republic, Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University Vienna, A-1090 Vienna, Austria, Institute for Ethnobiology, Playa Diana, San José/Petén, Guatemala, Department of Botany, Museum of Natural History, A-1010 Vienna, Austria, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, A-1090 Vienna, Austria, Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria
- Published online on: March 23, 2012 https://doi.org/10.3892/ijo.2012.1412
- Pages: 2131-2139
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Investigating the bioactivity of traditional medical remedies under the controlled conditions of a laboratory is an option to find additional applications, novel formulations or lead structures for the development of new drugs. The present work analysed the anti‑neoplastic activity of increasing polar extracts of the rainforest plant Critonia morifolia (Asteraceae) that has been successfully used as traditional remedy to treat various inflammatory conditions in the long-lasting medical tradition of the Central American Maya, which was here also confirmed in vitro. The apolar petroleum ether extract exhibited the most potent anti‑proliferative and pro‑apoptotic effects in HL‑60 cells and triggered down-regulation of Cdc25C and cyclin D1 within 30 min followed by the inhibition of c-Myc expression and the onset of caspase-3 activation within 2 h. Subsequent to these very rapid molecular responses Chk2 and H2AX became phosphorylated (γ‑H2AX) after 4 h. Analysis of the cell cycle distribution showed an accumulation of cells in the G2-M phase within 8 h and after 24 h in S-phase. This was temporally paralleled by the down-regulation of Cdc25A, Cdc25B, Wee1 and Akt. Therefore, the attenuation of cell cycle progression in the G2-M phase was consistent with the known role of Chk2 for G2-M arrest and with the role of Cdc25B in S-phase progression. These findings suggest the presence of two distinct active principles in the petroleum ether extract of C. moriflia. These facilitated the strong apoptotic response evidenced by the rapid activation of caspase-3 that was later enforced by the inhibition of the survival kinase Akt. Importantly, the efficient down-regulation of Akt, which is successfully tested in current clinical trials, is a unique property of C. morifolia.