Investigation of Antiproliferative Effects of Home-Made and Commercial Apple Vinegars on Myeloma Cells

Vinegar is an aqueous food product made by a succession of yeast and acetic acid bacteria activities from fruits that contain high carbohydrates such as apples and grapes. Vinegar has been used as a dietary spice and natural remedy since ancient times due to its therapeutic properties including antimicrobial, antidiabetic, and anticancer activities. It has been shown that some bioactive compounds exhibiting antioxidant activity in vinegars lead to anticancer activity. The aim of the present study was to investigate antiproliferative effect of commercial and home-made apple vinegars in native and neutralized form on myeloma cells. In order to neutralize the vinegars, sodium hydroxide (NaOH) was used. A serial two-fold dilutions of the vinegars (50%, 25%, 12.5%, 6.25%, 3.12%, 1.56%, 0.78%, 0.39%) prepared with cell medium were treated to the cells. The MTT (3-(4.5-Dimethylthiazol-2-yl)-2.5-Diphenyltetrazolium Bromide) assay was used to determine the cellular viability in the cells treated with the vinegars. In this study, while commercial vinegar possessed a stronger antiproliferative activity than home-made vinegar, all native vinegars possessed stronger antiproliferative effect than neutralized vinegars. Interestingly, when home-made vinegar (both native and neutralized) concentrations were from 6.25 to 1.56%, the cell viability increased. Apple vinegar exhibited antiproliferative activity on myeloma cells; however, further studies are required to clarify the mechanisms underlying this activity.

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (±)-codonopsinol B and its N-nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the trans-stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective α-chelation-controlled addition of vinyl-MgBr/CeCl3 to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding γ-amino-α,β-diol with aqueous hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr > 95:5). (±)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (±)-codonopsinol B and its N-nor-methyl analogue was evaluated using several cell line models.

Berberine Shows Proapoptotic Effect and Potentiation of Cytotoxic Drugs Acitivity in Colorectal Adenocarcinoma Cells

Colorectal cancer, despite advances in treatment and diagnosis, is one of the most common causes of death from cancer. Conventional anticancer treatment is associated with serious side effects, therefore, new strategies are needed to reduce its toxicity. Natural compound berberine has shown antiproliferative activity against various cancer cells including colon. To investigate antiproliferative effect of berberine in human colorectal adenocarcinoma cells and its ability to potentiate the effect of convenient cytostatics taxol, docetaxel, doxorubicin and cisplatin we used MTT assay and flow cytometry was used to detect its proapoptotic effect and effect on cell cycle. In our experiments we observed significant antiproliferative activity of berberine chloride with IC50= 6.7526 μM. Combination of berberine chloride (1μM) with taxol, docetaxel, doxorubicin and carboplatin significantly increased their antiproliferative activity and decreased their IC50 values. Cell cycle analysis revealed increase in sub-G0 /G1 fraction considered as apoptotic and very mild increase in G0/G1 fraction in berberine chloride (5μM) treated cells. proapoptotic effect of berberine chloride (5μM) was confirmed by Annexin V/PI staining. Based on our results, we can assume that berberine has antiproliferative effect and the combination of berberine with cytostatics could be a promising alternative treatment for cancer. Further studies are necesary to investigate the exact mechanisms of action and drug – drug interactions.

Antiproliferative effect of extracts and fractions of the root of Terminalia avicennioides (Combretaceae) Guill and Perr. on HepG2 and Vero cell lines

Background Terminalia avicennioides Guill and Perr (Combretaceae) is an important West African medicinal plant. The plant is used locally against microbes and parasites in both humans and animals and studies have demonstrated its cytotoxicity potential. Thus, this study was carried out to test the cytotoxic effect of the extracts and fractions of the root of the medicinal plant Terminalia avicennioides Guill and Perr (Combretaceae) in two different cell lines. Methods Methanol, ethanol, 30 % ethanol, hot water and cold water extracts and ethylacetate, hexane, chloroform, butanol and residual water fractions, were evaluated at 1000, 750, 500, 250, 100 and 50 µg/mL concentrations, with doxorubicin as positive control. The cells were incubated with the extracts for 48 h at 37 °C in a 5 % CO2 humidified incubator. The inhibition of cell viability, determined with the methyl blue thiazole tetrazolium bromide (MTT) assay, was used to assess the anti-proliferative effect of the extracts, in normal Vero Monkey kidney and human liver cancer (HepG2) cell lines. Results There was a concentration-dependent inhibition of cell viability in both the HepG2 and Vero cell lines. For HepG2 cells, antiproliferative effect was highest for the hexane fraction (viability ranged from 19.63 ± 1.10 % to 70.30 ± 1.78 % for 1000 and 50 µg/mL, respectively. For Vero cells, the highest antiproliferative effect, at 1000 µg/mL, was with hexane fraction (cell viability 21.37 ± 3.50 %), while at 50 µg/mL the chloroform fraction demonstrated the highest effect (viability of 86.10 ± 1.95 %). Conclusions The extracts and fractions from the root of Terminalia avicennioides have antiproliferative effect on the Vero and HepG2 cell lines tested. However, the extracts and fractions were not more toxic to the HepG2 than to the Vero cells. The cytotoxic effect of stem-bark and leaf extracts could be evaluated in the future to determine its anticancer potential.