Pholiotic acid promotes apoptosis in human metastatic melanoma cells.

Mushrooms produce a great variety of secondary metabolites that can be successful in both prevention and treatment of various cancers. In particular, higher Basidiomycete mushrooms contain various types of biologically active low-molecular compounds in fruiting bodies with suggested anticarcinogenic effects. The polyamine analogue {(2R)-2-[(S)-3-hydroxy-3-methylglutaryloxy] putrescine dicinnamamide} indicated with the name pholiotic acid, isolated for the first time by us from the fruiting bodies of the Basidiomycete Pholiota spumosa (Fr.) Sing. (Strophariaceae), inhibited the viability of human prostate cancer cells, such as other polyamine synthetic analogues that have shown antitumor activity in several types of cancer, including melanoma. Melanoma is an aggressive skin cancer that can metastasize to other organs and presents a high resistance to conventional therapies. In light of these considerations, the present study was therefore designed to assess whether this putrescine derivative could inhibit the growth of human metastatic melanoma cell lines, M14 and A2058. The results obtained demonstrate that this natural compound, at 12.5-50 µM concentration, was able to reduce cell viability of both cancer cells inducing cell death by intrinsic apoptotic pathway that probably involves PTEN activity, inhibition of Hsp70 expression and reactive oxygen species production. On the other hand, the increased expression of enzymes involved in polyamine catabolism trigger apoptotic cell death leading to polyamine depletion and generation of reactive oxygen species as by-products. In conclusion, these findings, starting point for further investigation, implement available our data to support pholiotic acid as an attractive potential chemopreventive agent, and provide a basis for further research into the use of this polyamine derivative as potential anticancer agent for melanoma in combination with existing therapies to improve treatment efficacy and overcome the obstacle of drug resistance.

Zornia latifolia: a smart drug being adulterated by Stylosanthes guianensis.

Dried herbal preparations, based on "Zornia latifolia," are commonly sold on web, mainly for their supposed hallucinogenic properties. In this work, we demonstrate that these commercial products contain a different Fabacea, i.e., Stylosanthes guianensis, a cheaper plant, widely cultivated in tropical regions as a fodder legume. We were provided with plant samples of true Zornia latifolia from Brazil, and carried out a thorough comparison of the two species. The assignment of commercial samples was performed by means of micro-morphological analysis, DNA barcoding, and partial phytochemical investigation. We observed that Z. latifolia contains large amounts of flavonoid di-glycosides derived from luteolin, apigenin, and genistein, while in S. guianensis lesser amounts of flavonoids, mainly derived from quercetin, were found. It is likely that the spasmolytic and anxiolytic properties of Z. latifolia, as reported in traditional medicine, derive from its contents in apigenin and/or genistein.

Putrescine-1,4-dicinnamide from Pholiota spumosa (Basidiomycetes) inhibits cell growth of human prostate cancer cells.

Previously, it was isolated from the fruiting bodies of the gilled mushroom Pholiota spumosa (Basidiomycetes, Strophariaceae), putrescine-1,4-dicinnamide, a phenylpropanoid derivative conjugated with polyamine putrescine never isolated before as a natural compound. Recently, polyamine analogs that are similar in structure to the natural polyamines but that cannot mimic their functions that are essential for cellular growth and differentiation, have shown antitumor activity in several types of human cancer cells. Therefore, we have now investigated the response of DU-145 cells, a well characterized androgen-independent human prostate cancer (PCA) cell line, to this phenylpropanoid derivative. The results presented here demonstrate that putrescine-1,4-dicinnamide, as suggested for polyamine analogs synthesized artificially, inhibits the cell growth of cancer cells inducing apoptosis cell death, mediated, at least in part, by the activation of caspase cascades, that at higher doses shift to necrosis, through the increase of reactive oxygen species (ROS) generation.

Ab initio and density functional evaluations of the molecular conformations of beta-caryophyllene and 6-hydroxycaryophyllene.

The four conformations of beta-caryophyllene (alphaalpha, alphabeta, betaalpha, and betabeta) were investigated ab initio at the 6-31G/HF and MP2 levels and additionally with density functional methods (B3LYP/6-31G), as it concerns their relative thermodynamic stabilities. The alphaalpha is predicted to be the most stable geometry, in agreement with low-temperature NMR measurements. In the case of 6-hydroxycaryophyllene, the alphaalpha is still the most stable conformation when the configuration at C-6 is S, but when the configuration is reversed to R the betabeta geometry becomes the most stable one. This is again in agreement with NMR data. On the other hand, for both molecules the AM1 semiempirical model Hamiltonian fails to predict the alphaalpha as a low-energy geometry, mainly due to an incorrect description of the cyclobutane ring puckering. The interconversion paths among the different minima are also analyzed and discussed. The solvent effect (either chloroform or water) on the stability of the different conformers of beta-caryophyllene and 6-hydroxycaryophyllene was studied in the polarizable continuum model framework.