Sensitisation of ovarian cancer cells to cisplatin by flavonoids from Scutellaria barbata.

Combination of natural components with anticancer drugs is a new strategy for cancer chemotherapy to increase antitumour responses. In this study, we investigated the sensitisation effects of nine flavonoids from Scutellaria barbata to cisplatin (CDDP) on human ovarian cancer cells. The combinations of three flavonoids with CDDP showed the synergistic effects. The intracellular reactive oxygen species and the antioxidant activity were measured. The data suggest that the synergistic effects of flavonoids with CDDP on ovarian cancer cells did not directly correlate with their redox properties, but could be associated with the positions of hydroxyl group and methoxy group of flavonoids.

Emodin regulates apoptotic pathway in human liver cancer cells.

Emodin, a natural anthraquinone, has been reported to possess antiproliferative effects in many cancer cell lines. However, anticancer mechanism against human liver cancer remains unclear. In this study, we observed that emodin induced apoptosis in HepG2 cells and caused a significant accumulation of cells in the G1 phase. Western blot data showed that emodin treatment caused the increasing of release of cytochrome c into cytosol from mitochondria and the activation of caspase-8 and caspase-9, which suggest that the intrinsic and extrinsic pathways could be involved. Emodin treatment also resulted in a dose-dependent accumulation of intracellular reactive oxygen species. Furthermore, emodin increased the protein level of p53 and decreased the protein level of NF-κB/p65 in HepG2 cells, which indicated these two regulators might play a role in emodin-induced apoptosis. Computational modeling showed that emodin could directly bind to the BH3 domain of Bcl-2 through forming one hydrogen bond with Ala146 residue in Bcl-2. From these examinations, emodin not only significantly downregulated expression of Bcl-2 but also inhibited the heterodimerization of Bcl-2 with Bax because of strong interaction between emodin and Bcl-2. These suggest that emodin induces apoptosis in liver cancer cell line through a multifaceted complex cascade of events.

Alantolactone induces activation of apoptosis in human hepatoma cells.

Alantolactone, a sesquiterpene lactone, possesses anti-inflammatory property. In this study, we provide evidence that it could be developed as a novel agent against human liver cancer. We observed that alantolactone treatment to HepG2, Bel-7402 and SMMC-7721 cells, human liver cancer cell lines resulted in a dose-dependent inhibition of cell growth. We selected HepG2 cell line as a test model system. Alantolactone treatment of HepG2 cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via modulating the protein levels of Bcl-2 family and activation of caspases. Moreover, caspase-8 and Bid activation, loss of mitochondrial transmembrane potential and cytochrome c release suggest the existence of a cross-talk between the death receptor and the mitochondrial pathways. We also observed that alantolactone treatment of cells resulted in a dose-dependent decrease in NF- κB/p65. In addition, a significant and progressive increase in the level of p53 protein in alantolactone-treated cells was observed. Taken together, our data suggest that alantolactone could be developed as an agent against human liver cancer.

Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line.

Dianthus superbus L. is commonly used as a traditional Chinese medicine. We recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D. superbus exhibited the strongest antioxidant and cytotoxic activities. In this study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS (20-80 µg/ml) for 48 h led to a significant dose-dependent increase in the percentage of cells in sub-G1 phase by analysis of the content of DNA in cells, and a large number of apoptotic bodies containing nuclear fragments were observed in cells treated with 80 µg/ml of EE-DS for 24 h by using Hoechst 33258 staining. These data show that EE-DS can induce apoptosis of HepG2 cells. Immunoblot analysis showed that EE-DS significantly suppressed the expressions of Bcl-2 and NF-κB. Treatment of cells with EE-DS (80 µg/ml) for 48 h resulted in significant increase of cytochrome c in the cytosol, which indicated cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also determined when the cells treated with EE-DS. The results suggest that apoptosis of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic pathway. High performance liquid chromatography (HPLC) data showed that the composition of EE-DS is complicated. Further studies are needed to find the effective constituents of EE-DS.

Anticancer, antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel.

This study was designed to examine the anticancer, antioxidant and antimicrobial activities of the essential oil from Lycopus lucidus Turcz. var. hirtus Regel. The essential oil treatment to six human cancer cell lines resulted in a dose-dependent inhibition of cell growth. The cytotoxicity of the essential oil on liver carcinoma and breast cancer cell lines was significantly stronger than on other cell lines. The essential oil can induce apoptosis of the liver carcinoma cell line Bel-7402 and decrease the intracellular GSH level. The antioxidant effect of the essential oil was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH) scavenging assays. The essential oil exhibited moderate antioxidant activity. The antimicrobial activity of the essential oil was evaluated against eight microorganisms using the disc diffusion and broth microdilution methods. The essential oil also showed moderate antimicrobial activity. These suggest that the essential oil could hold a good potential for use in the pharmaceutical industry.

Changes in mitochondrial membrane potential and reactive oxygen species during wogonin-induced cell death in human hepatoma cells.

Flavonoids exist extensively in plants, and several biological effects of them have been demonstrated. Wogonin is an important flavonoid compound. In this study, wogonin showed obvious growth inhibition on Bel-7402 cells. The major mechanisms of inhibition included cell apoptosis and cytotoxic effects. Wogonin-induced cell death showed characteristics of apoptosis including DNA fragmentation, chromatin condensation, appearance of apoptotic bodies, and an increase in hypodiploid cells. However, the percentage of necrosis cells also increased with the increase of wogonin concentration. Furthermore, treatment with wogonin caused changes of reactive oxygen species (ROS) and mitochondrial membrane potentials (DeltaPsim, MMP), the decrease of the ratio of reduced and oxidized glutathione (GSH/GSSG), cytochrome c release and activation of caspase-9.

Composition, antimicrobial activity and cytotoxicity of essential oils from Aristolochia mollissima.

The compositions of the essential oils from the rhizome and the aerial part of Aristolochia mollissima were analysed by GC-MS, 68 constituents (88.2% of the total oil) and 74 constituents (89.4% of the total oil) were identified, respectively. 2,2,7,7-Tetramethyltricyclo[6.2.1.0(1,6)]undec-4-en-3-one was the most abundant constituent among all in the ratios of 15.9% and 13.5% from the rhizome and the aerial part of A. mollissima, respectively. Among other main compounds, (E)-ß-santalol acetate (10.3%) and camphene (6.7%) were detected in the rhizome oil, spathulenol (6.8%) was detected in the oil from the aerial par of A. mollissima. The antimicrobial activity of the essential oils from the rhizome and the aerial part of A. mollissima was evaluated against 20 microorganisms using disc diffusion and broth microdilution methods. The gram-positive bacteria were more sensitive to both oils than gram-negative bacteria and yeasts. The rhizome oil showed the strongest bactericidal activity against Staphylococcus saprophyticus, whereas the oil from the aerial part of A. mollissima exerted the strongest bactericidal activity against methicillin-resistant and methicillin-senstive Staphylococcus aureus. The in vitro cytotoxicity of both oils on six human cancer cell lines were also examined. The cytotoxicity of the rhizome oil on four cancer cell lines (ACHN, Bel-7402, Hep G2 and HeLa) was significantly stronger than that of the oil from the aerial part of A. mollissima.