Antiproliferative and toxicological properties of drimanes obtained from Drimys brasiliensis stem barks.

Stem barks of Drimys brasiliensis (Winteraceae) are consumed by the population in the form of a condiment. It is widely used to treat gastric and stomach problems and also to treat cancer. The extracts have demonstrated antiproliferative, antileishmanial and antimicrobial activities assigned to drimane sesquiterpenes. This study aimed to optimize the extraction conditions of the drimanes sesquiterpenes identified as 1-ß-(p-coumaroyloxy)-polygodial 1, drimanial 2 and 1-ß-(p-methoxycinnamoyl)-polygodial 3 in stem bark extracts. The HPLC-DAD method was developed and validated for the quantification of drimanes 1-3. The cytotoxic activity of these drimanes in human cancer cells, and the toxicological effects of the hydroethanolic extract, were determined. The extracts were prepared using different extractive conditions (solvents, plant: solvent ratio and time). The cytotoxicity effect was evaluated against leukemia, lymphomas, carcinomas and sarcomas cells using the tetrazolium assay (MTT). Furthermore, the acute toxicity was determined by measuring the biochemical parameters and by histopathological analysis. The hemolytic activity and micronucleus test were also performed. The method was linear, sensitive, precise and accurate for both drimanes 1-3. The best condition for extraction was using dichloromethane with plant: solvent proportion 1:10 (w/v) for six hours under dynamic maceration. Isolated drimanes exhibited cytotoxic effects with IC50 values ​​ranging from 0.13 to 112.67 µM. Compound 1 demonstrated significant results for acute promyelocytic leukemia (NB4) and Burkitt's lymphoma (RAMOS) cells while driamane 3 for Burkitt's lymphoma (RAJI) and acute T cell leukemia (MOLT4) cells. No signs of toxicity was observed and neither was mutagenicity or hemolytic activity.

Antitumor activities of Quercetin and Green Tea in xenografts of human leukemia HL60 cells.

Quercetin is one of the most abundant flavonoids, present in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Green tea is a widely consumed beverage, known for a potential source of free radical scavenging and anti-cancer activities. Herein, we investigate the in vivo antitumor efficacy of quercetin and green tea in human leukemia. Human tumors were xenografted into NOD/SCID mice. Quercetin and green tea reduced tumor growth in HL-60 xenografts accompanied by decreased expression of anti-apoptotic proteins, BCL-2, BCL-XL and MCL-1 and increased expression of BAX, a pro-apoptotic protein. Moreover, caspase-3 was activated to a greater extent after quercetin and green tea treatment. Quercetin and green tea also mediated G1 phase cell cycle arrest in HL-60 xenografts. Treatment with quercetin and green tea induced conversion of LC3-I to LC3-II as well as activation of autophagy proteins, suggesting that quercetin and green tea initiate the autophagic progression. We have provided evidence that quercetin and green tea induces signaling at the level of apoptosis, cell cycle and autophagy which converge to antigrowth effects in HL-60 xenograft mice suggesting that these compounds may be a compelling ally in cancer treatment.