2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells.

BACKGROUND: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. MATERIALS AND METHODS: T47D human breast cancer cells were treated with 2-deoxy- D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent- phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. RESULTS: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. CONCLUSIONS: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

Dandelion (Taraxacum officinale) decreases male rat fertility in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum officinale (L.) Weber ex F.H. Wigg. is commonly used in Jordan folk medicine for the treatment of panophthalmitis, chronic constipation, and diabetes. In addition, herbalists prescribe the aqueous extract of Taraxacum officinale to enhance male's fertility. The current work was undertaken to investigate the validity and/or invalidity of the aqueous extract of Taraxacum officinale on enhancing the reproductive activity in male rat. MATERIALS AND METHODS: Thirty three adult male rats were divided into three groups. Experimental groups received the aqueous extract of Taraxacum officinale orally for 60 days in two different sublethal doses; 1/10 LD(50) as high dose and 1/20 LD(50) as low dose, whereas the control group received distilled water. RESULTS: The administration of the aqueous extract of Taraxacum officinale resulted in a significant decrease in testis weight in the two experimental groups in comparison to the control group but had no effect on body or organ weight. The extract of this plant caused a decrease of the following in the two experimental groups, compared to the control group: sperm count, motility and normal morphology, pregnancy rate and diameter and wall thickness of seminiferous tubules. Also, distortion of morphology of the seminiferous tubules and arrest in spermatogenesis was observed in the experimental groups. In addition, the percentage of sperm with damaged chromatin integrity was significantly higher in the two experimental groups. CONCLUSIONS: From the present study, we can conclude that the aqueous extract of Taraxacum officinale acts as an anti-fertility agent rather than a fertility booster as prescribed by Jordanian herbalists.