20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action

We recently isolated 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer

Multiple Changes in Peptide and Lipid Expression Associated with Regeneration in the Nervous System of the Medicinal Leech

peer reviewe

Strategies for the Use of Fallback Foods in Apes

Researchers have suggested that fallback foods (FBFs) shape primate food processing adaptations, whereas preferred foods drive harvesting adaptations, and that the dietary importance of FBFs is central in determining the expression of a variety of traits. We examine these hypotheses in extant apes. First, we compare the nature and dietary importance of FBFs used by each taxon. FBF importance appears greatest in gorillas, followed by chimpanzees and siamangs, and least in orangutans and gibbons (bonobos are difficult to place). Next, we compare 20 traits among taxa to assess whether the relative expression of traits expected for consumption of FBFs matches their observed dietary importance. Trait manifestation generally conforms to predictions based on dietary importance of FBFs. However, some departures from predictions exist, particularly for orang-utans, which express relatively more food harvesting and processing traits predicted for consuming large amounts of FBFs than expected based on observed dietary importance. This is probably due to the chemical, mechanical, and phenological properties of the apes’ main FBFs, in particular high importance of figs for chimpanzees and hylobatids, compared to use of bark and leaves—plus figs in at least some Sumatran populations—by orang-utans. This may have permitted more specialized harvesting adaptations in chimpanzees and hylobatids, and required enhanced processing adaptations in orang-utans. Possible intercontinental differences in the availability and quality of preferred and FBFs may also be important. Our analysis supports previous hypotheses suggesting a critical influence of the dietary importance and quality of FBFs on ape ecology and, consequently, evolution

Screening for paclitaxel and other taxanes in kernel and shell of Corylus avellana (Hazelnut)

Interestingly, paclitaxel was found in shells and leaves of hazelnut plant Corylus avellana. The aim of this present work was to verify whether hazelnut kernel contained paclitaxel. Hazelnut kernels were obtained from two places (local market and Oregon, USA) were analyzed by HPLC-MS. Paclitaxel and other taxanes 10-deacetylbaccatin III, Baccatin III, 10-deacetyl-7-xylosylcephalomannine, 10-deacetyl-7- xylosylpaclitaxel, 10-deacetylpaclitaxel, 7-xylosylpaclitaxel, Cephalomanine, 10-deacetyl-7- epipaclitaxel, 7-epi-paclitaxel were analyzed based on m/z value of molecular ion but none was found except for molecular ion of m/z=854 in the crude extract of kernel from a local market and shell from Oregon, US. The molecular ion was suspected belonging to 7-epi-paclitaxel, an isomer of paclitaxel. 7- epi-paclitaxel could be present in the extract of kernel and shell of tested varieties in this study. Paclitaxel was not detected it could have degraded during sampling process or the tested varieties did not produce paclitaxel or was too low to be detected.fals