Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities

One newly (1) and 10 known oleanane-type triterpenoids (2-11) were isolated from the methanol extract of Panax stipuleanatus rhizomes. Based on their spectroscopic data, these compounds were identified as spinasaponin A methyl ester (1), pesudoginsenoside RP1 methyl ester (2), spinasaponin A 28-O-glucoside (3), pseudoginsenoside RT1 methyl ester (4), pseudoginsenoside RT1 (5), stipuleanoside R-2 methyl ester (6), stipuleanoside R2 (7), araloside A methyl ester (8), 3-O-beta-D-glucopyranosyl (1 -> 3)-beta-D-glucuronopyranoside-28-O-beta-D-glucopyranosyl oleanolic acid methyl ester (9), 3-O-beta-D-xylopyranosyl (1 -> 2)-beta-D-glucopyranosyl-28-O-beta-D-glucopyranosyl oleanolic acid (10), and chikusetsusaponin IVa (11). When the cytotoxic activities of the isolated compounds were evaluated, compound 1 exhibited significant cytotoxic activity with IC50 values of 4.44 and 0.63 mu M against HL-60 (leukemia) and HCT-116 (colon cancer) cell lines, respectively. Compound 2 showed potent cytotoxicity with an IC50 of 6.50 mu M against HCT-116, whereas it was less cytotoxic against HL-60 (IC50 = 41.45 mu M). After HL-60 and HCT-116 were treated with compounds 1 and 2, increased production of apoptotic bodies was observed. Furthermore, compounds 1 and 2 in HCT-116 cells activated intrinsic and extrinsic apoptosis pathways by upregulating DR-5 and Bax, downregulating Bcl-2, activating caspase-9, and cleaving poly-ADP-ribose polymerase (PARP). We also observed the activation of ERK1/2 MAPK by both compounds in the HCT-116 cells. Together, compounds 1 and 2 might induce intrinsic and extrinsic apoptosis pathways through the activation of the ERK1/2 MAPK pathway in HCT-116 colon cancer cells. Structure-activity relationship analysis indicated that a carboxyl group at position-28 is potentially responsible for the cytotoxic effects. (C) 2010 Elsevier Ltd. All rights reserved.