Anticancer effect of a new benzophenanthridine isolated from Zanthoxylum madagascariense (Rutaceline).
Fractionation of the cyclohexane extract from the stem bark powder of Zanthoxylum madagascariense led to the isolation of a new benzophenanthridine-type alkaloid, hydrochloride of 2,3-methylendioxy-8-hydroxy- 7-methoxy-benzo[C]phenanthridine (Rutaceline), characterized on the basis of its spectral data. Rutaceline was evaluated for its antiproliferative capacity on the human colorectal adenocarcinoma (Caco-2) and the African green monkey kidney (Vero) cell lines. The 50% inhibition of cell growth (IC50) obtained after 24 h incubation was similar for both cells lines (110-115 microg/ml, i.e. 269-281 microM), but at 48 h the IC50 value for the Caco-2 cells was lower than for the Vero cells (20 microg/lml, i.e. 49 microM versus 90 microg/ml, i.e. 220 microM) indicating a higher cell growth inhibitory effect on the colon adenocarcinoma cells. At the respective IC50 concentrations, Rutaceline did not significantly induce apoptosis but induced cell cycle arrest in the GO/G1 phase, as well as a decrease of cells in S phase. Rutaceline also induced DNA fragmentation in both cell lines, as revealed by agarose gel electrophoresis, and a dose-dependent clastogenic effect in both cell lines as revealed by the Comet assay.
Pachon
G
G
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain.
Rasoanaivo
H
H
Azqueta
A
A
Rakotozafy
J C
JC
Raharisololalao
A
A
De Cerain
A López
AL
De Lapuente
J
J
Borràs
M
M
Moukha
S
S
Centelles
J J
JJ
Creppy
E E
EE
Cascante
M
M
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015179:Colorectal Neoplasms; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D008270:Madagascar; D014709:Vero Cells; D032106:Zanthoxylum
D000970:Antineoplastic Agents; D053119:Benzophenanthridines