Cancer Chemopreventive Effects of Cycloartane-Type and Related Triterpenoids in in Vitro and in Vivo Models

Abstract

Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Triterpene glycosides and other polar constituents of shea (Vitellaria paradoxa) kernels and their bioactivities

“…The protocols of assay of melanin content, in vitro EBV-EA activation experiment, determination of DPPH free-radical-scavenging activity, assay of TPA-induced ear-edema inflammation in mice, cytotoxicity assay, Annexin V-propidium iodide (PI) double staining, and Western blot analysis Akihisa et al, 2006Akihisa et al, , 2007Akihisa et al, , 2010aKikuchi et al, 2007Kikuchi et al, , 2011Tabata et al, 2005) were described in Supplementary data (S2).…”

A review of the taxonomy, ethnobotany, chemistry and pharmacology of Sutherlandia frutescens (Fabaceae)

“…Furthermore, it is now also known that the major triterpenoids of Sutherlandia are structurally closely related to cycloartane-type triterpenoids with proven cancer chemopreventive activity (Kikuchi et al, 2007).…”

“…The possibility that canavanine is not the only active compound is supported by Kikuchi et al (2007), who studied the cancer chemopreventive activity of 48 natural and semisynthetic cycloartane-type triterpenoids. Many of the compounds (so-called astragalosides) are known from the genus Astragalus L., also a member of the tribe Galegeae and related to Sutherlandia.…”

In vitro effects of Sutherlandia frutescens water extracts on cell numbers, morphology, cell cycle progression and cell death in a tumorigenic and a non-tumorigenic epithelial breast cell line

“…Other biologically active compounds of interest are flavonol glycosides and triterpenoid saponins including the discovery of four new cycloartane glycosides, sutherlandiosides A-D, as well as SU1 which is the major triterpene in commercial Sutherlandia material (Fu et al, 2008;Van Wyk and Albrecht, 2008). Kikuchi et al (2007) demonstrated that cycloartane-type triterpenoids with a hydroxy group at C-24 in the side chain are possible chemopreventive agents in chemical carcinogenesis (Kikuchi et al, 2007). Sutherlandiosides A-D as well as SU1 have a hydroxyl moiety at the C-24 position, thus it would be of great interest to test these compounds for biological activity (Fu et al, 2008;Van Wyk and Albrecht, 2008).…”