Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities

Abstract

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 RP 1 methyl ester ( 2), spinasaponin A 28- O-glucoside ( 3), pseudoginsenoside RT 1 methyl ester ( 4), pseudoginsenoside RT 1 ( 5), stipuleanoside R 2 methyl ester ( 6), stipuleanoside R 2 ( 7), araloside A methyl ester ( 8), 3- O-β- d-glucopyranosyl (1→3)-β- d-glucuronopyranoside-28- O-β- d-glucopyranosyl oleanolic acid methyl ester ( 9), 3- O-β- d-xylopyranosyl (1→2)-β- d-glucopyranosyl-28- O-β- 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 IC 50 values of 4.44 and 0.63 μM against HL-60 (leukemia) and HCT-116 (colon cancer) cell lines, respectively. Compound 2 showed potent cytotoxicity with an IC 50 of 6.50 μM against HCT-116, whereas it was less cytotoxic against HL-60 (IC 50 = 41.45 μM). 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.