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 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.
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Chun
C
Liang
Yan
Y
Ding
Huu Tung
HT
Nguyen
Jeong-Ah
JA
Kim
Hye-Jin
HJ
Boo
Hee-Kyoung
HK
Kang
Mahn Cuong
MC
Nguyen
Young Ho
YH
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts; D015398:Signal Transduction / Q000187:drug effects; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D014315:Triterpenes; C413246:oleanane; D009828:Oleanolic Acid