No abstract

The hollow fiber test has been developed for the preliminary in vivo assessment of cancer chemotherapeutic efficacy of selected natural products. Using this model, we have established growth conditions for HL-60, HUVEC, Ishikawa, KB, KB-V1, LNCaP, Lu1, MCF-7, Mel2, P-388, and SW626 cells implanted at the intraperitoneal (i.p.) and subcutaneous (s.c.) compartments of athymic mice. Five cytotoxic natural product isolates (2-6) were tested in this model, along with paclitaxel (taxol) (1). Among the compounds tested, dioscin (2) and 13-methoxy-15-oxozoapatlin (3) were found to be active, indicating their potential to function as cancer chemotherapeutic agents. On the other hand, ochraceolide A (4), alpha-lapachone (5), and 2-(1-hydroxyethyl)naphtha[2,3-b]furan-4,9-quinone (6), all of which were significantly cytotoxic to cultured mammalian cells, did not mediate significant responses with the hollow fiber model. In further xenograft studies using KB cells implanted at the subcutaneous site, compound 3 mediated a statistically significant response which was consistent with the response observed at the subcutaneous compartment in the hollow fiber tests. In sum, these studies illustrate the usefulness of the hollow fiber model in natural product drug discovery programs. Preliminary indications of potential therapeutic efficacy can be provided quickly at relatively low expense. Agents capable of mediating a response at the subcutaneous site would appear to warrant greatest attention.

Sasa borealis (Poaceae) is a perennial medicinal plant which is a major source of bamboo leaves in Korea. The n-BuOH extract of S. borealis leaves exhibited significant antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and a cytoprotective effect against oxidative damage in HepG2 cells. Bioactivity-guided fractionation by column chromatography led to the isolation of two antioxidative flavonoid C-glycoside derivatives, isoorientin (2) and isoorientin 2"-O-alpha-L-rhamnoside (4) along with tricin 7-O-beta-D-glucopyranoside (1) and apigenin 6-C-beta-D-xylopyranosyl-8-C-beta-D-glucopyranoside (3). Their structures were identified on the basis of chemical and spectroscopic methods. The radical scavenging activity and cytoprotective effect against oxidative damage of all the isolated compounds were also evaluated. Isoorientin (2) and isoorientin 2-O-alpha-L-rhamnoside (4) showed potent free radical scavenging activity with IC50 values of 9.5 and 34.5 microM, respectively, and strong cytoprotective effects against t-BOOH-induced oxidative damage in HepG2 cells, at very low concentrations of 1.1 microM isoorientin and 0.8 microM isoorientin 2-O-alpha-L-rhamnoside. This is the first report of the isolation and antioxidant activity of compounds 2 and 4 from S. borealis.