In vitro anti-cancer activity of two ethno-pharmacological healing plants from Guatemala Pluchea odorata and Phlebodium decumanum.
Many traditional healing plants successfully passed several hundred years of empirical testing against specific diseases and thereby demonstrating that they are well tolerated in humans. Although quite a few ethno-pharmacological plants are applied against a variety of conditions there are still numerous plants that have not been cross-tested in diseases apart from the traditional applications. Herein we demonstrate the anti-neoplastic potential of two healing plants used by the Maya of the Guatemala/Belize area against severe inflammatory conditions such as neuritis, rheumatism, arthritis, coughs, bruises and tumours. Phlebodium decumanum and Pluchea odorata were collected, dried and freeze dried, and extracted with five solvents of increasing polarity. We tested HL-60 and MCF-7 cells, the inhibition of proliferation and the induction of cell death were investigated as hallmark endpoints to measure the efficiency of anti-cancer drugs. Western blot and FACS analyses elucidated the underlying mechanisms. While extracts of P. decumanum showed only moderate anti-cancer activity and were therefore not further analysed, particularly the dichloromethane extract of P. odorata inhibited the cell cycle in G2-M which correlated with the activation of checkpoint kinase 2, and down-regulation of Cdc25A and cyclin D1 as well as inactivation of Erk1/2. In HL-60 and MCF-7 cells this extract was a very strong inducer of cell death activating caspase-3 followed by PARP signature type cleavage. The initiating death trigger was likely the stabilization of microtubules monitored by the rapid acetylation of alpha-tubulin, which was even more pronounced than that triggered by taxol. The dichloromethane extract of P. odorata contains apolar constituents which inhibit inflammatory responses and exhibit anti-cancer activity. The strong proapoptotic potential warrants further bioassay-guided fractionation to discover and test the active principle(s).
Gridling
Manuela
M
Institute of Clinical Pathology, Medical University of Vienna, A-1090 Vienna, Austria.
Stark
Nicole
N
Madlener
Sibylle
S
Lackner
Andreas
A
Popescu
Ruxandra
R
Benedek
Birgit
B
Diaz
Rene
R
Tut
Foster M
FM
Nha Vo
Thanh Phuong
TP
Huber
Daniela
D
Gollinger
Michaela
M
Saiko
Philipp
P
Ozmen
Ali
A
Mosgoeller
Wilhelm
W
De Martin
Rainer
R
Eytner
Ruth
R
Wagner
Karl-Heinz
KH
Grusch
Michael
M
Fritzer-Szekeres
Monika
M
Szekeres
Thomas
T
Kopp
Brigitte
B
Frisch
Richard
R
Krupitza
Georg
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019659:Asteraceae; D006690:Bisbenzimidazole / Q000494:pharmacology; D045744:Cell Line, Tumor; D002469:Cell Separation; D004354:Drug Screening Assays, Antitumor; D019040:E-Selectin / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D020834:Ethnopharmacology / Q000379:methods; D005434:Flow Cytometry; D006166:Guatemala; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D010936:Plant Extracts / Q000494:pharmacology*; D013347:Subcellular Fractions
D000970:Antineoplastic Agents; D019040:E-Selectin; D010936:Plant Extracts; D006690:Bisbenzimidazole