Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen).
Bioassay-guided fractionation of a chloroform-soluble extract of Garcinia mangostana stem bark, using the HT-29 human colon cancer cell line and an enzyme-based ELISA NF-kappaB assay, led to the isolation of a new xanthone, 11-hydroxy-3-O-methyl-1-isomangostin (1). The structure of 1 was elucidated by spectroscopic data analysis. In addition, 10 other known compounds, 11-hydroxy-1-isomangostin (2), 11alpha-mangostanin (3), 3-isomangostin (4), alpha-mangostin (5), beta-mangostin (6), garcinone D (7), 9-hydroxycalabaxanthone (8), 8-deoxygartanin (9), gartanin (10), and cratoxyxanthone (11), were isolated. Compounds 4-8 exhibited cytotoxicity against the HT-29 cell line with ED50 values of 4.9, 1.7, 1.7, 2.3, and 9.1 microM, respectively. In an ELISA NF-kappaB assay, compounds 5-7, 9, and 10 inhibited p65 activation with IC50 values of 15.9, 12.1, 3.2, 11.3, and 19.0 microM, respectively, and 6 showed p50 inhibitory activity with an IC50 value of 7.5 microM. Alpha-mangostin (5) was further tested in an in vivo hollow fiber assay, using HT-29, LNCaP, and MCF-7 cells, but it was found to be inactive at the highest dose tested (20 mg/kg).
College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Ah-Reum
AR
Han
Jeong-Ah
JA
Kim
Daniel D
DD
Lantvit
Leonardus B S
LB
Kardono
Soedarsono
S
Riswan
Heebyung
H
Chai
Esperanza J
EJ
Carcache de Blanco
Norman R
NR
Farnsworth
Steven M
SM
Swanson
A Douglas
AD
Kinghorn
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D029762:Garcinia mangostana / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007214:Indonesia; D008954:Models, Biological; D010946:Plants, Medicinal / Q000737:chemistry*; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
C545413:11-hydroxy-3-O-methyl-1-isomangostin; D000972:Antineoplastic Agents, Phytogenic; D044004:Xanthones