The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.

The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor ß was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted.

Methanol extract of the ethnopharmaceutical remedy Smilax spinosa exhibits anti-neoplastic activity.

Plants have been the source of several effective drugs for the treatment of cancer and over 60% of anticancer drugs originate from natural sources. Therefore, extracts of the rhizome of Smilax spinosa, an ethnomedicinal plant from Guatemala which is used for the treatment of inflammatory conditions, were investigated regarding their anti-neoplastic activities. By using several solvents the methanol extract was by far the most potent against HL60 cell proliferation (50% inhibition at 60 µg/ml). Furthermore, fractionation of this extract yielded fraction F2, which exhibited enforced pro-apoptotic activity, and activated CYP1A1. Proteins that are relevant for cell cycle progression and apoptosis, as well as proto-oncogenes were investigated by western blotting. This revealed that the methanol extract increased the levels of p21 and this may have caused cell cycle attenuation. The derivative fraction F2 induced apoptosis through the intrinsic pathway, which correlated with the inhibition of Stat3 phosphorylation and concomitant induction of caspase 9, then caspase 8 and caspase 3. In summary, the methanol extract and the derivative fraction F2 of S. spinosa showed anti-neoplastic effects in HL-60 cells and CYP1A1 activation in estrogen receptor-positive MCF-7 breast cancer cells but not in estrogen-negative MDA-MB231 breast cancer cells. Based on our data Smilax spinosa may be a promising source for novel anticancer agents.

An apolar extract of Critonia morifolia inhibits c-Myc, cyclin D1, Cdc25A, Cdc25B, Cdc25C and Akt and induces apoptosis.

Investigating the bioactivity of traditional medical remedies under the controlled conditions of a laboratory is an option to find additional applications, novel formulations or lead structures for the development of new drugs. The present work analysed the anti­neoplastic activity of increasing polar extracts of the rainforest plant Critonia morifolia (Asteraceae) that has been successfully used as traditional remedy to treat various inflammatory conditions in the long-lasting medical tradition of the Central American Maya, which was here also confirmed in vitro. The apolar petroleum ether extract exhibited the most potent anti­proliferative and pro­apoptotic effects in HL­60 cells and triggered down-regulation of Cdc25C and cyclin D1 within 30 min followed by the inhibition of c-Myc expression and the onset of caspase-3 activation within 2 h. Subsequent to these very rapid molecular responses Chk2 and H2AX became phosphorylated (γ­H2AX) after 4 h. Analysis of the cell cycle distribution showed an accumulation of cells in the G2-M phase within 8 h and after 24 h in S-phase. This was temporally paralleled by the down-regulation of Cdc25A, Cdc25B, Wee1 and Akt. Therefore, the attenuation of cell cycle progression in the G2-M phase was consistent with the known role of Chk2 for G2-M arrest and with the role of Cdc25B in S-phase progression. These findings suggest the presence of two distinct active principles in the petroleum ether extract of C. moriflia. These facilitated the strong apoptotic response evidenced by the rapid activation of caspase-3 that was later enforced by the inhibition of the survival kinase Akt. Importantly, the efficient down-regulation of Akt, which is successfully tested in current clinical trials, is a unique property of C. morifolia.

Separation of anti-neoplastic activities by fractionation of a Pluchea odorata extract.

Natural products continue to represent the main source for therapeutics, and ethnopharmacological remedies from high biodiversity regions are a rich source for the development of novel drugs. Hence, in our attempt to find new anti-neoplastic activities we focused on ethno-medicinal plants of the Maya, who live in the world's third richest area in vascular plant species. Pluchea odorata (Asteraceae) is traditionally used for the treatment of various inflammatory disorders and recently, the in vitro anti-cancer activities of different extracts of this plant were described. Here, we present the results of bioassay-guided fractionations of the dichloromethane extract of P. odorata that aimed to enrich the active principles. The separation resulted in fractions which showed the dissociation of two distinct anti-neoplastic mechanisms; firstly, a genotoxic effect that was accompanied by tubulin polymerization, cell cycle arrest, and apoptosis (fraction F2/11), and secondly, an effect that interfered with the orchestrated expression of Cyclin D1, Cdc25A, and Cdc2 and that also led to cell cycle arrest and apoptosis (fraction F3/4). Thus, the elimination of generally toxic properties and beyond that the development of active principles of P. odorata, which disturb cancer cell cycle progression, are of interest for potential future therapeutic concepts against proliferative diseases.

A multi-locus plastid phylogenetic analysis of the pantropical genus Diospyros (Ebenaceae), with an emphasis on the radiation and biogeographic origins of the New Caledonian endemic species.

We aimed to clarify phylogenetic relationships within the pantropical genus Diospyros (Ebenaceae sensulato), and ascertain biogeographical patterns in the New Caledonian endemic species. We used DNA sequences from eight plastid regions (rbcL, atpB, matK, ndhF, trnK intron, trnL intron, trnL-trnF spacer, and trnS-trnG spacer) and included 149 accessions representing 119 Diospyros species in our analysis. Results from this study confirmed the monophyly of Diospyros with good support and provided a clearer picture of the relationships within the genus than in previous studies. Evidence from phylogenetic analyses suggests that Diospyros colonized New Caledonia multiple times. The four lineages of Diospyros in New Caledonia also differ in their degree of diversification. The molecular data indicate that one lineage is paleoendemic and derived from an ancient Australian species. The other three lineages are more closely related to several Southeast Asian species; two of them are neoendemics, and one has radiated rapidly and recently.

Generic delimitation and relationships in Ebenaceae sensu lato: evidence from six plastid DNA regions.

Phylogenetic relationships of the pantropical family Ebenaceae s.l. were investigated using plastid DNA sequence data from six regions: atpB, matK, ndhF, trnK intron, trnL intron, and trnL-trnF spacer. Sampling included representatives of all currently recognized genera of Ebenaceae, Diospyros, Euclea, and Lissocarpa, and nearly all taxa that were previously recognized at the generic level, e.g., Cargillia, Gunisanthus, Maba, Macreightia, Royena, and Tetraclis. Our results strongly support monophyly of Ebenaceae s.l. and demonstrate that the previous infrafamilar classifications of the family do not circumscribe monophyletic groups. A new infrafamilial classification based on a phylogenetic approach is proposed here and consists of two subfamilies, Lissocarpoideae and Ebenoideae, and four genera, Lissocarpa, Euclea, Royena, and Diospyros. Relationships and potential synapomorphic characters are discussed and summarized. This study supports a western Gondwanan origin of family and indicates that both vicariant and long-distance dispersal events played an important role in attaining current distributions.