Further drimane sesquiterpenes from Drimys brasiliensis stem barks with cytotoxic potential.

Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activitys and evaluates them in leukemia cells. The stem bark extract were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1ß-O-p-methoxy-E-cinnamoyl-5α-keto-11α-enol-albicanol (1a) and the isomer 1ß-O-p-methoxy-E-cinnamoyl-5α-keto-11ß-enol-albicanol (1b) and 1ß-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), the mixture drimanial (5) and 1ß-O-(p-methoxy-E-cinnamoyl)-6α-hydroxypolygodial (6) were also isolated. The drimanes (1-4) and drimanial (5), 1ß-(p-coumaroyloxy)-polygodial (7), 1ß-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 µM. 1-ß-(p-cumaroiloxi)-polygodial showed the best result with IC50 8.18 and 3.56 µM by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-12.

Cytotoxic, antitumour and antimetastatic activity of two new polyacetylenes isolated from Vernonia scorpioides (Lam.) Pers.

Vernonia scorpioides (Lam.) Pers., popularly known as Enxuga, Erva-de-São Simão and Piracá, has been used in folk medicine for its anti-inflammatory, wound healing and antimicrobial properties. Two polyacetylenes, 5-octa-2,4,6-triynyl-furan-2(5H)-one (1) and 8'-hydroxy 3-4 dihydrovernoniyne (2), were isolated from the dichloromethane extract fraction of V. scorpioides. In this study, polyacetylene 1 demonstrated a more potent cytotoxic activity than 2 in the tumour cell lines examined, and cytotoxicity was found to be comparable to a commercial drug (p > 0.05) in melanoma cells. No significant cytotoxic effect was observed in normal cell lines. Furthermore, polyacetylene 1 induced an in vitro increase in caspase-3 activity in B16F10 cells. When polyacetylene 1 was administered intraperitoneally (i.p.) in mice, a reduction in solid tumour volume and metastasis was observed in mice injected with B16F10 cells. An increase in locomotor activity was also observed in mice with solid tumours, and an inhibition of mechanical hypersensitivity was observed in a mouse model of metastasis. Notably, no significant morphological change was observed in several organs harvested from the treated mice. In conclusion, in vitro and in vivo anticancer activity of polyacetylene 1 was consistently observed and involved the induction of apoptosis by the activation of caspase-3. The anticancer activity demonstrated by polyacetylene 1, together with the absence of preliminary toxicological effects, represents a new and interesting option for the management of neoplastic disease.

Comparison of effects of the ethanolic extracts of brazilian propolis on human leukemic cells as assessed with the MTT assay.

Propolis is a resinous product collected by honey bees. It was also reported that propolis has a wide variety of biological actions, including antimicrobial activity and antioxidant, anti-inflammatory, and suppressive effects of dioxin toxicity activities. The aim of this study was to compare the in vitro cytotoxic activities of green propolis (G12) and red propolis (G13) in human leukemia cells. These cells were incubated with different concentrations of propolis and 48 hours after the IC(50) was calculated for each cell. The results showed that the red propolis has cytotoxic effect in vitro higher than green propolis. Red propolis was showed to be cytostatic in K562 cells and caused the same amount of apoptosis as its control Gleevec. In conclusion, these results showed that red propolis is more cytotoxic than the green propolis in a variety of human cell lines of leukemia. Red propolis may contain drugs capable of inhibiting cancer cell growth. Therefore, further isolation of respective chemical ingredients from the red propolis (G13) for identification of the activities is necessary.

Evaluation of the anti-proliferative effect the extracts of Allamanda blanchetti and A. schottii on the growth of leukemic and endothelial cells.

PURPOSE: To investigate the anti-proliferative effect of A. blanchetti and A. schottii extracts. METHODS: The anti-proliferative effect of A. blanchetti and A. schottii ethanolic extracts on K562 leukemic cells as well as on BMEC and HUVEC were evaluated. Phytochemical analysis to identify the possible active components was carried out. RESULTS: The root extract of A. schottii was the most active of them. At 80 microg/mL, the root extracts showed a cytostatic effect on K562, whereas at 400 microg/mL, there was a strong cytotoxic effect. Similar cytostatic and cytotoxic effects were seen in the endothelial cells, but at lower doses. The effect of A. schottii root extract on endothelial cells was seen at concentrations ten times lower (8 microg/mL) than the effect of the A. blanchetti root extract (80 microg/mL). Phytochemical investigation of different fractions and parts of the plant led to the isolation of several known compounds, some of which are described for the first time in the genus Allamanda, and with previous evidence of anticancer and antitumoral properties. CONCLUSIONS: Our results suggest that both plants studied exhibit cytostatic and cytotoxic activity, but the most active compounds are located in the roots.