Cytotoxic activities of alkaloid constituents from the climbing stems and rhizomes of Sinomenium acutum against cancer stem cells.

From the methanolic extract of the climbing stems and rhizomes of Sinomenium acutum, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/ß-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC50 values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/ß-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/ß-catenin pathway.

Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells.

We isolated seven new iridoid glucosides (valerianairidoids I-VII; 1-3, 6, 7, 9, and 12) and six known compounds from the methanol extract of the dried rhizomes and roots of Valeriana fauriei. Chemical and spectroscopic data were used to elucidate the chemical structures of the seven new iridoid glucosides, and their absolute configurations were determined by comparing their electronic circular dichroism (ECD) spectra with those determined experimentally. Aglycones 1a, 6a, and 9a, which were obtained by enzymatic hydrolysis of the isolated iridoid glucosides, exhibited anti-proliferative activities against cancer stem cells (CSCs) established by a sphere-formation assay using human breast cancer (MDA-MB-231) and human astrocytoma (U-251MG) cells. Interestingly, these iridoids selectively showed anti-proliferative activities against CSCs from MDA-MB-231 cells. These results suggest that the iridoids obtained in this study may have potency as a breast cancer treatment and as preventive agent via exterminating CSCs.

Chemical structures and induction of cell death via heat shock protein inhibition of the prenylated phloroglucinol derivatives isolated from Hypericum erectum.

Four new prenylated phloroglucinol derivatives (+)-erectumol I (1a), (-)-erectumol I (1b), (-)-erectumol II (2a), and (+)-erectumol II (2b) were isolated from the methanol extracts of the whole plants of Hypericum erectum. These new compounds were isolated as a pair of enantiomers, respectively. The planar chemical structures and relative configurations of the new compounds were suggested by Cu-Kα X-ray diffraction analysis and been confirmed by high-resolution mass and 1D and 2D NMR spectroscopic data. The absolute configuration of the four new compounds were established by comparing the experimental and predicted electronic circular dichroism data. Isolated compounds 1b and 2b induced death of Adriamycin-treated HeLa cells. Their enantiomers 1a and 2a did not. In addition, the apparent mechanism of cell death of 1b was the inhibited expression of heat shock protein 105.

Cell death-inducing activities via Hsp inhibition of the sesquiterpenes isolated from Valeriana fauriei.

Three new sesquiterpenes, valerianaterpenes I-III, and eight known compounds have been isolated from the methanol extract of the rhizomes and roots of Valeriana fauriei. The chemical structures of the three new sesquiterpenes were elucidated based on chemical and spectroscopic evidence. The absolute stereochemistry of valerianaterpene I was determined using X-ray crystallography. The cell death-inducing activity of isolated compounds alone or combination with Adriamycin (ADR) was observed by time-lapse cell imaging. Although the isolated compounds did not affect the number of mitotic entry cells and dead cells alone, kessyl glycol, kessyl glycol diacetate, and iso-teucladiol significantly increased the number of dead cells on ADR treated human cervical cancer cells. One of the mechanisms of cell death-inducing activity for the kessyl glycol acetate was suggested to be the inhibition of heat-shock protein 105 (Hsp105) expression level. This paper first deals with the naturally occurring compounds as Hsp105 inhibitor.

Limonoids isolated from the Fortunella crassifolia and the Citrus junos with their cell death-inducing activity on Adriamycin-treated cancer cell.

From the fruits of Fortunella crassifolia and the peels of Citrus junos, two new limonoids, fortunellone and junosol were isolated together with three known compounds including nomilin. The chemical structures of the new compounds were elucidated based on chemical/physicochemical evidence. For fortunellone, the absolute configuration was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Fortunellon and nomilin significantly increased the number of dead cells on adriamycin (ADR)-treated human cervical cancer cells (HeLa). On the other hand, fortunellon and nomilin did not affects the number of dead cells alone. These results suggested that fortunellone and nomilin may have the potency as the chemotherapy enhancement agents.