Anti-cancer stem cell activity of a sesquiterpene lactone isolated from Ambrosia arborescens and of a synthetic derivative.

New regimens are constantly being pursued in cancer treatment, especially in the context of treatment-resistant cancer stem cells (CSCs) that are assumed to be involved in cancer recurrence. Here, we investigated the anti-cancer activity of sesquiterpene lactones (SLs) isolated from Ambrosia arborescens and of synthetic derivatives in breast cancer cell lines, with a specific focus on activity against CSCs. The breast cancer cell lines MCF-7, JIMT-1, and HCC1937 and the normal-like breast epithelial cell line MCF-10A were treated with the SLs damsin and coronopilin, isolated from A. arborescens, and with ambrosin and dindol-01, synthesized using damsin. Inhibitory concentration 50 (IC50) values were obtained from dose-response curves. Based on IC50 values, doses in the µM range were used for investigating effects on cell proliferation, cell cycle phase distribution, cell death, micronuclei formation, and cell migration. Western blot analysis was used to investigate proteins involved in cell cycle regulation as well as in the NF-κB pathway since SLs have been shown to inhibit this transcription factor. Specific CSC effects were investigated using three CSC assays. All compounds inhibited cell proliferation; however, damsin and ambrosin were toxic at single-digit micromolar ranges, while higher concentrations were required for coronopilin and dindol-01. Of the four cell lines, the compounds had the least effect on the normal-like MCF-10A cells. The inhibition of cell proliferation can partly be explained by downregulation of cyclin-dependent kinase 2. All compounds inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53. Treatment with damsin and ambrosin decreased the CSC subpopulation and inhibited cell migration. Our results suggest that these compounds should be further investigated to find efficient CSC-inhibiting compounds.

Antioxidant and antimutagenic polyisoprenylated benzophenones and xanthones from Rheedia acuminata.

Dichloromethane extract of the stem bark of Rheedia acuminata yielded three benzophenones with antioxidant activity, the new one named acuminophenone A (1), guttiferone K (2) and isoxanthochymol (3), along with the known xanthones formoxanthone C (4) and macluraxanthone (5). The structures were established through interpretation of their spectroscopic data, the stereochemistry of compounds (1) and (2) were resolved by experimental and computational experiments and their antioxidant activities were measured using the DPPH, ABTS and TEAC assays. The antioxidant results showed that metabolites 1, 4 and 5 had a better antioxidant activity than the reference compound quercetin. In addition, we evaluate the mutagenicity and antimutagenicity of the CH2Cl2 extract as well as of the free radical scavenger compounds 1, 4 and 5 by the AMES Salmonella/microsomal test. No mutagenicity was found in the CH2Cl2 extract using Salmonella typhimurium strains TA98, TA100, TA102, TA1537 and TA1538, with or without S9 metabolic activation. The pure compounds neither showed mutagenicity in TA 102 strain and the most important result was the strong reduction of mutagenic effect induced by hydrogen peroxide in S. typhimurium TA102, with or without S9, showed by the compounds 1 (more than 93%) and 4 (more than 88%) at 0.02 microg/plate.

Antiproliferative effects of curcuphenol, a sesquiterpene phenol.

Curcuphenol is a sesquiterpene isolated from sponges and plants having several significant biological activities. The present study explored its effect on cell proliferation and apoptosis in Caco-2 human colon cancer cells. It was demonstrated that curcuphenol in concentrations in the range of 29-116 µg/ml inhibited cell proliferation and DNA replication and induced cell death in a dose-dependent manner. The induction of apoptosis was associated with a stimulation of the activity of caspase-3. The findings presented here suggest that curcuphenol has antiproliferative and pro-apoptotic properties.

Actividad Genotóxica de Opuntia soehrensii, evaluada por el Test de Mutación y Recombinación Somática en D. melanogaster / Genotoxic Activity of Opuntia soehrensii, evaluated by the Test of Mutation and Somatic Recombination in D. melanogaster

El extracto acuoso de Opuntia soehrensii, planta medicinal utilizada como antiviral en la farmacopea boliviana fue evaluado en su capacidad genotóxica por el test SMART en alas de D. melanogaster. Por tratarse de un extracto entero se evaluó por dos cruces diferentes; el cruce estandar y el cruce de Alta Bioactivación. Los resultados muestran que Opuntia soeherensii no es genotóxica en concentraciones de 3.57 mg/ml y 7.4 mg/ml para ninguno de los dos cruces, pero es promutagénica a 1.78 mg/ml.

Evaluación genotoxicológica del extracto etéreo de baccharis incarum / Genotoxicológica evaluation of the ethereal extract of Baccharis incarum

La genotoxidad del extracto etéreo de Baccharis incarum, una planta utilizada en la medicina tradicional boliviana, ha sido evaluada por el test de Mutación y Recombinación Somática en alas de Drosophila melanogaster. Este extracto no es genotóxico de acción indirecta.

Genotoxicidad/ antigenotoxicidad de Bacharis latifolia / Genotoxicity/antigenotoxicity of Bacharis latifolia

El potencial genotóxico y antigenotóxico del extracto diclorometánico de Bacharis latifolia fue evaluado por el Test de Mutación y Recombinación Somática (SMART) en alas de Drosophila melanogaster usando dos diferentes cruces. Los resultados muestran que B.latifolia no es genotóxica ni antigenotóxica. La presencia de flavonoides en su composición química corroboran su actividad fotoprotectora.