Brazilian Green Propolis: Chemical Composition of Essential Oil and Their In Vitro Antioxidant, Antibacterial and Antiproliferative Activities

Abstract Propolis is a resinous substance collected and processed by Apis mellifera from parts of plants, buds and exudates. In Minas Gerais (MG) state, Brazil, green propolis is produced from the collection of resinous substance found in shoot apices of Baccharis dracunculifolia. This paper aims to investigate the chemical composition and in vitro antioxidant, anti-Helicobacter pylori, antimycobacterial and antiproliferative activities of essential oil (EO) from Brazilian green propolis (BGP-EO). The oil showed high antibacterial activity against H. pylori (MIC = 6.25 µg/mL), Mycobacterium avium (MIC = 62.5 µg/mL) and M. tuberculosis (MIC = 64 µg/mL). Its antioxidant activity was evaluated in vitro by both DPPH (IC50 = 23.48 µg/mL) and ABTS (IC50 = 32.18 µg/mL) methods. The antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor cell lines (MCF-7, HeLa and M059J) was analyzed by the XTT assay. BGP-EO showed inhibition of normal cell growth at 68.93 ± 2.56 µg/mL. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were 56.17, 66.43 and -65.83 µg/mL for MCF-7, HeLa and M059J cells, respectively. Its major constituents, which were determined by GC-FID and GC-MS, were carvacrol (20.7 %), acetophenone (13.5 %), spathulenol (11.0 %), (E)-nerolidol (9.7 %) and β-caryophyllene (6.2 %). These results showed the effectiveness of BGP-EO as a natural product which has promising biological activities.

Syntheses of alkyl-de-sanguinarine-N5-methyl derivatives and evaluation of in vitro growth inhibitory activities against cancer cell lines / 药学学报

2,3:7,8-Bis(methylenedioxy)benzo[c]phenanthridine was synthesized in a strategy of converging synthesis with 6-bromo-2,3-dihydroxybenzaldehyde, 5-nitronaphthalene-2,3-diol, and dibromomethane, respectively, as starting materials. The reaction process included dioxy-de-dibromo nucleophilic substitution under alkaline condition, reduction reaction, Schiff base-forming reaction, and an arene radical cyclization step under the presence of Bu3SnH and AIBN as radical initiator, among others. The 2,3:7,8-bis(methylenedioxy)benzo[c] phenanthridine as intermediate was reacted with NaBH4 and different aliphatic acids as alkylation agent to afford 2,3:7,8-bis(methylenedioxy)-5,6-dihydro-N5-alkylbenzo[c]phenanthridines. These dihydro-type products were aromatized using DDQ as oxidant under alkaline condition, and then, salinized using HCl as source of equilibrium anion to yield the series of target alkyl-de-sanguinarine-N5-methyl derivatives. All the synthesized alkyl-de-sanguinarine-N5-methyl derivatives exhibited significantly improved in vitro growth inhibitory activities against cancer cell lines as compared with sanguinarine and the positive control. In pharmacological experiments targeting five cancer cell lines, the target compounds showed activities five-fold active than that of sanguinarine. The findings of this study indicated that the structure modification strategy of substituting n-alkyls for the N5-methyl of natural sanguinarine can be used to improve the growth inhibitory activities against cancer cell lines through increasing liposolubility and steric hindrance to protect the active 5,6-imine structure.

In vivo and in vitro anti-tumor activity studies of five sesquiterpenoids from Inula helenium / 中国药理学通报

Aim To detect the antitumor activities of five sesquiterpene lactones from the roots of Inula helenium.Method Using MTT assay to evaluate the antitumor activities of five sesquiterpene lactones to the cell lines of U251SP,T-98,HLE,MM1-CB,HMV-1 and KT,and to explore the relationship between structure and activities.Results Isoalantolactone exhibited significant anti-growth activities to U251SP,HLE and MM1-CB,while other compounds demonstrated weak or moderate anti-growth activities to cell lines even in the 50% inhibition concentration≤100 μmol·L~(-1).Conclusion Isoalantolactone exhibits significant anti-growth activities to three cell lines and its anti-tumor activitiesve close relationship with the structures,α,β-unsaturated five-membered lactone ring is necessary for the activities,and saturated lactone or 5,10-seco and A,B-ring become a ten-membered macro-ring leading to the loss or decrease of anti-growth activity.

The Relationship between the MICA/B Expression on Cancer Cell Lines and Their Sensitivity to NK Cell Cytotoxicity / 中国医科大学学报

Objective To analyze the relationship between the expression of MHC class I chain-related gene A/B(MICA/B) on different human cancer cells and their sensitivity to NK cell cytotoxicity.Methods Hie expression MICA/B in K562,Bcap37,769P and A549 cells was measured by FACS.Isolation of NK cells were obtained by the modified RosetteSep~((R)) procedure.Cytotoxicity of NK cells at different ef0.50)%,(90.72±0.64)%,(55.59±0.55)%,and(3.84±0.10)% respectively.The purity of NK cells obtained by the modified RosetteSep~((R)) procedure was(96.52±2.42)%,whereas the cytotoxicity of NK cells against K562,Bcap39 and 769P was much higher than that of A549(P<0.01).The expression of MICA/B was significantly correlated with the cytotoxicity of NK cells at E:T ratios of 5:1,10:1 and 20:1 respectively(P<0.01).Conclusion The MICA/B expression on cancer cell lines was correlated with NK cell-mediated cytolysis and influenced the cytotoxicity of NK cells.

Expressions of Cell Cycle Control Genes in Human Uterine Cervical Cancer Cells / 대한암학회지

PURPOSE: Recently, many aspects of biological functions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors and Rb gene have been reported, and the cell cycle control genes are considered to act important roles in tumorigenesis. In this study, the expression patterns of major cell cycle control genes (cyclin A, B, C, Dl, E, E2F, p16INK4a, p21WAF1 and Rb) in various human cervical cancer cells were analysed to elucidate the impacts of the cell cycle control genes on the carcinogenesis of human cervical cancer. MATERIALS AND METHODS: The expression patterns of major cell cycle control genes in HT-3, C33-A, HeLa, C4-II, SiHa and CaSki human uterine cervical cancer cells were analysed by using western blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In most of the cervical cancer cells tested, the overexpressions of cyclin A, E, E2F and markedly decreased expression of Rb tumor suppressor proteins were observed. By comparing RNA and protein expressions in each cancer cells, the mechanisms of increased expressions of cyclin A, E and decreased expression of Rb were elucidated as post-translational controls. CONCLUSION: The cervical carcinogenesis caused by the altered expressions of the major cell cycle control genes can be hypothesized as follows: overexpressions of cyclin E and A cause acceleration of Rb phosphorylations and E2F overexpression; increased E2F function accelerates G1/S transition of the cells; compensatory increase of p16 expression cannot stop the cells in Gl phase because Rb expression is severely decreased; consequently, loss of Rb function, 61 shortening, inappropriate cell division and decreased function of the maintenance of genomic stability occur. In addition to these alterations, loss of p53 functions further accelerate instability of genome and decrease the sus- ceptability to cell death. Furthermore, overexpression of Bc12 protects these abnormal cells from apoptosis. All these derangements of cell cycle control should contribute to the human cervical carcinogenesis.