title: An apolar extract of Critonia morifolia inhibits c-Myc, cyclin D1, Cdc25A,             Cdc25B, Cdc25C and Akt and induces apoptosis.
abstract: 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.
authors.affiliation: Institute of Clinical Pathology, Medical University of Vienna,                     Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Unger
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Popescu
authors.forename: Benedikt
authors.initials: B
authors.lastname: Giessrigl
authors.forename: Lucie
authors.initials: L
authors.lastname: Rarova
authors.forename: Irene
authors.initials: I
authors.lastname: Herbacek
authors.forename: Mareike
authors.initials: M
authors.lastname: Seelinger
authors.forename: Rene
authors.initials: R
authors.lastname: Diaz
authors.forename: Bruno
authors.initials: B
authors.lastname: Wallnöfer
authors.forename: Monika
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: Thomas
authors.initials: T
authors.lastname: Szekeres
authors.forename: Richard
authors.initials: R
authors.lastname: Frisch
authors.forename: Karel
authors.initials: K
authors.lastname: Doležal
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
authors.forename: Rainer
authors.initials: R
authors.lastname: De Martin
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kopp
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
mesh_terms: D000473:Alkanes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D000473:Alkanes; D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D018797:Cell Cycle Proteins; C489427:MYC protein, human; D010936:Plant Extracts; D016271:Proto-Oncogene Proteins c-myc; D012997:Solvents; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; C517004:CDC25A protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C004544:naphtha