Two Novel Triterpenoids with Antiproliferative and Apoptotic Activities in Human Leukemia Cells Isolated from the Resin of Garcinia hanburyi

Abstract

Two new triterpenoids, 2α-hydroxy-3β-O-acetyllup-20(29)-en-28-oic acid (1) and 3-O-(4′-O-acetyl)-α-L-arabinopyranosyloleanolic acid (2), together with two known triterpenoids, betulinic acid (3) and messagenic acid (4) were isolated from the CHCl₃ extract of Garcinia hanburyi resin. The structures were elucidated by analysis of the NMR spectroscopic data. The antiproliferative effects and the apoptosis induction abilities of compounds 1 and 2 were determined in four human leukemia cell lines. Compound 2 was more potent than compound 1 in inhibiting cell growth with IC₅₀ values of 2.45, 2.69, 2.42, and 4.15 μM in HL-60, NB4, U937 and K562 cells, respectively.

Key words

Garcinia hanburyi - Guttiferae - triterpenoids - antiproliferative activity - apoptosis - leukemia

References

• 1 Sukpondma Y, Rukachaisirikul V, Phongpaichit S. Antibacterial caged-tetraprenylated xanthones from the fruits of Garcinia hanburyi.  Chem Pharm Bull. 2005;  53 850-2
• 2 Han Q B, Wang Y L, Yang L, Tso T F, Qiao C F, Song J Z. et al . Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi.  Chem Pharm Bull. 2006;  54 265-7
• 3 Reutrakul V, Anantachoke N, Pohmakotr M, Jaipetch T, Sophasan S, Kasisit J. et al . Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi.  Planta Med. 2007;  73 33-40
• 4 Asano T, Chiba K, Tada M, Yoshii T. Cytotoxic xanthones from Garcinia hanburyi.  Phytochemistry. 1996;  41 815-20
• 5 Han Q B, Wang Y L, Yang L, Tso T F, Qiao C F, Song J Z. et al . A pair of novel cytotoxic polyprenylated xanthone epimers from Gamboges.  ChemBiodivers. 2006;  3 101-5
• 6 Lv G B, Yang X X, Huang Q S. The isolation and structure of neo-gambogic acid from Garcinia hanburyi.  Acta Pharm Sin. 1984;  19 636-9
• 7 Han Q B, Yang L, Liu Y, Wang Y L, Qiao C F, Song J Z. et al . Gambogic acid and epigambogic acid, C-2 epimers with novel anticancer effects from Garcinia hanburyi.  Planta Med. 2006;  72 281-4
• 8 Siddiqui S, Hafeez F, Begum S, Siddiqui B S. Oleanderol, a new pentacyclic triterpene from the leaves of Nerium oleander.  J Nat Prod. 1988;  51 229-33
• 9 Macias F A, Simonet A M, Galindo J CG. Natural products as allelochemical. 5. Bioactive steroids and triterpenes from Melilotus messanensis and their allelopathic potential.  J Chem Ecol. 1997;  23 1781-5
• 10 Kumar N S, Muthukuda P M, Wazeer M IM. A lupenediol from Euonymus revolutus.  Phytochemistry. 1985;  24 1337-40
• 11 Kojima H, Ogura H. Configurational studies on hydroxy group at C-2, 3 and 23 or 24 of oleanene and ursene-type triterpenes by NMR spectroscopy.  Phytochemistry. 1989;  28 1703-10
• 12 Seo S, Tomita Y, Tori K. Carbon-13 NMR spectra of urs-12-enes and application to structural assignments of components of Isodon japonicus Hara tissue cultures. Tetrahedron Lett 1975: 7-10
• 13 Seo S, Tomita Y, Tori K. Biosynthesis of ursene-type triterpenes from sodium [1,2 – ¹³C] acetate in tissue cultures of Isodon japonicus Hara and reassignments of ¹³C NMR signals in urs-12-enes.  J Chem Soc Chem Commun. 1975;  23 954-6
• 14 Yu S S, Yu D Q, Liang X T. Triterpenoid saponins from the bark of Nothopanax davidii.  Phytochemistry. 1995;  38 695-8
• 15 Aoki T, Suga T. Triterpenoid saponins from the flower buds of Fatsia japonica.  Phytochemistry. 1978;  17 771-3
• 16 Poon K H, Zhang J X, Wang C, Tse A KW, Wan C K, Fong W F. Betulinic acid enhances 1alpha, 25-dihydroxyvitamin D₃-induced differentiation in human HL-60 promyelocytic leukemia cells.  Anticancer Drugs. 2004;  15 619-24
• 17 Wang F, Hua H M, Pei Y H, Chen D, Jing Y K. Triterpenoids from the resin of Styrax tonkinensis and their antiproliferative and differentiation effects in human leukemia HL-60 cells.  J Nat Prod. 2006;  69 807-10
• 18 Ehrhardt H, Fulda S, Fuehrer M, Debatin K M, Jeremias I. Betulinic acid-induced apoptosis in leukemia cells.  Leukemia. 2004;  18 1406-12
• 19 Ji Z N, Ye W C, Liu G G, Hsiao W LW. 23-Hydroxybetulinic acid-mediated apoptosis is accompanied by decrease in Bcl-2 expression and telomerase activity in HL-60 cells.  Life Sci. 2002;  72 1-9
• 20 Zhong L, Li P, Han J, Qu G Q, Guo D. Structure-activity relationships of saponins from Gleditsia sinensis in cytotoxicity and induction of apoptosis.  Planta Med. 2004;  70 797-802
• 21 Yu S S, Xiao Z Y. The phytochemical investigation on Nothopanax davidii.  Acta Pharm Sin. 1991;  26 261-6
• 22 Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R. NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3).  Blood. 1991;  77 1080-4
• 23 Jing Y K, Dai J, Chalmers-Redman R ME, Tatton W GT, Waxman S. Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway.  Blood. 1999;  94 2102-11
• 24 Liu D, Song D D, Guo G, Wang R, Lv J L, Jing Y K. et al . The synthesis of 18β-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells.  Bioorg Med Chem. 2007;  15 5432-9