The cytotoxicity of 21 flavonoids and 5 sesquiterpene lactones, as present in Arnica species, was studied in GLC4, a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. Following continuous incubation, most flavonoids showed moderate to low cytotoxicity, as compared with the reference compound cisplatin (IC50 = 1.1 microM against GLC4 and 2.9 microM against COLO 320). Their IC50 values varied from 17 to > 200 microM. The most toxic compound was the flavone jaceosidin. Of the sesquiterpene lactones tested, helenalin, possessing both the reactive alpha-methylene-gamma-lactone moiety and a reactive alpha,beta-unsubstituted cyclopentenone ring, displayed the strongest cytotoxicity. For 2 h exposure, its IC50 value was 0.44 microM against GLC4 and 1.0 microM against COLO 320. COLO 320 was more sensitive than GLC4 for many flavonoids (especially for flavones), but more resistant to the cytotoxic effect of the sesquiterpene lactones bearing an exocylic methylene group fused to the lactone function.

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Extractive fermentation is a technique used to reduce end product inhibition by removing the fermentation products in situ. The extraction can be performed by using an organic/aqueous two-phase system if the organic phase ex-hibits the following desirable properties: -biocompatibility; -non-biodegradability; -advantageous distribution coefficient for the product to be extracted; -thermal and chemical stability. Chemical permeabilization of plant cell membranes as well as metabolite extraction into an organic phase can be both affected by the potential toxicity of the compound(s) used. A good predictor of the cell viability retention is 'log P', i.e. the logarithm of the solvent partition coefficient in a standard two-phase system octanollwater. Solvents with log P > 5 were found to be not toxic for plant cell suspension cultures of Modnda citrifolia 1 and, among them, hexadecane (log P = 8.8) was selected as the main extractive component. In this study, an organic/aqueous two-liquid-phase system was used to obtain the extraction of hydrophobic plant cell secondary metabolites. The selected compounds are the pigments anthraquinones, produced in high yields by cell suspension cultures of M. citrifolia (Rubiaceae). The organic phase consisted of a mixture of solvent plus co-solvent (hexadecane plus heptanol) 2. Cell viability was retained over the whole growth period.