2-3-5-4--tetrahydroxystilbene-2-o-glucopyranoside and Breast-Neoplasms

Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4'-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Docetaxel; Doxorubicin; Drug Resistance, Neoplasm; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Glucosides; Humans; MCF-7 Cells; Stilbenes; Zebrafish

Breast cancer has been reported to be a serious disease and a threat to women's health. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is a bioactive natural compound originating from. MTT assay was detected to determine cell viability. Furthermore, cell apoptosis was tested by flow cytometry and TUNEL assay. In addition, protein expression was measured by Western blot analysis.. The individual treatment of THSG and ADM induced cell injury. Moreover, cotreatment further increased it, which the effect may be associated with the elevation of the apoptotic-related protein expression such as Bax/Bcl-2 and cleaved caspase-3/caspase-3. Lastly, our results also show the reduction of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt protein expression in the individual or synergistic treatment.. Taken together, cotreatment of THSG and ADM may exert a synergistic reduction of cell injury via the inhibition of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt pathway. Thus, THSG might possess potent anti-breast cancer effect with ADM.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Breast Neoplasms; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Female; Glucosides; Humans; MCF-7 Cells; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; Stilbenes; Vascular Endothelial Growth Factor A

Although doxorubicin (Dox)-induced cardiac toxicity and pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) were reported to be correlated with reactive oxygen species (ROS) generation, there is no effective preventive treatment at present. Therefore, the aim of this study was to investigate whether antioxidants-resveratrol (RSVL), tetrahydroxystilbene glucoside (THSG), curcumin, and the ethanolic extract of Antrodia cinnamomea (EEAC)-have the ability to reduce Dox-induced ROS and have a synergistic anticancer effect with Dox that could prevent those side effects and enhance the efficacy of cancer treatment.. 3T3 normal cells were used as a model to evaluate the effects of these antioxidants in reducing ROS accumulation. Furthermore, the synergistic anticancer effect of antioxidants with Dox on the MCF-7 breast cancer model was also evaluated.. Pretreatment of cells with RSVL, curcumin, and EEAC increased the cell antioxidant ability by improving the activity of superoxide dismutase (SOD), prevented or limited intracellular damage, and ameliorated the harmful effects of ROS. Additionally, RSVL, curcumin, and EEAC had synergistic effects with Dox against MCF-7 breast cancer cells.. RSVL, curcumin, and EEAC have the potential to be clinically applied to prevent cardiac toxicity and HFS and enhance the anticancer efficiency of Dox.

Topics: 3T3 Cells; Animals; Antibiotics, Antineoplastic; Antioxidants; Antrodia; Breast Neoplasms; Complementary Therapies; Curcumin; Doxorubicin; Drug Synergism; Female; Glucosides; Humans; MCF-7 Cells; Mice; Plant Extracts; Reactive Oxygen Species; Resveratrol; Stilbenes; Superoxide Dismutase