IntroductionPaclitaxel (Taxol®) is a microtubule-targeted agent that is widely used for cancer treatment. However, resistance to paclitaxel is frequently encountered in the clinic. There is increasing interest in identifying compounds that may increase the sensitivity to conventional chemotherapeutic agents. In this study, we investigated whether green tea polyphenol (-)-epigallocatechin gallate (EGCG) could sensitize breast carcinoma to paclitaxel in vivo.MethodsBreast cancer cells were treated with or without EGCG and paclitaxel followed by detection of cell survival and apoptosis. c-Jun NH2-terminal kinase (JNK) phosphorylation and glucose-regulated protein 78 (GRP78) expression were detected by Western blotting. For in vivo study, 4T1 breast cancer cells were inoculated into Balb/c mice to establish a transplantation model. The tumor-bearing mice were treated with or without EGCG (30 mg/kg, i.p.) and paclitaxel (10 mg/kg, i.p.). Tumor growth was monitored. Apoptosis in tumor tissues was detected. Cell lysates from tumors were subjected to Western blot analysis of GRP78 expression and JNK phosphorylation.ResultsEGCG synergistically sensitized breast cancer cells to paclitaxel in vitro and in vivo. EGCG in combination with paclitaxel significantly induced 4T1 cells apoptosis compared with each single treatment. When tumor-bearing mice were treated with paclitaxel in combination with EGCG, tumor growth was significantly inhibited, whereas the single-agent activity for paclitaxel or EGCG was poor. EGCG overcame paclitaxel-induced GRP78 expression and potentiated paclitaxel-induced JNK phosphorylation in 4T1 cells both in vitro and in vivo.ConclusionsEGCG may be used as a sensitizer to enhance the cytotoxicity of paclitaxel.
The effect of commercial sterilization treatments on the levels of advanced glycation endproducts (AGEs) in meats was investigated. The amounts of both free and protein-bound N(ε)-carboxymethyllysine (CML) and N(ε)-carboxyethyllysine (CEL) in beef (rump, ribeye, short plate), pork (hind leg, tenderloin, belly), and chicken (chicken breasts, drumsticks) were determined using an HPLC-MS/MS method. Beef and pork had a small proportion (raw <15%; sterilized <8%) of free AGEs compared to the total AGEs, but raw chicken breasts had very high levels of free CEL (7.12±9.98 mg/kg; n=13) with large biological variation compared to pork (0.19±0.09 mg/kg; n=9) and beef (0.44±0.19 mg/kg; n=9). Commercial sterilization (121°C for 10 min) did not significantly affect the amounts of free CML or CEL, but led to about 0.6- to 3.6-fold increase of protein-bound CML and CEL. The amounts of protein and fat content in beef or pork had very little effect on the formation of protein-bound AGEs during sterilization process.
2,4-D retards senescence of postharvest citrus fruits by increasing exogenous auxin, endogenous ABA and SA contents, while decreasing ethylene production; and enhancing stress-defense capability through changing epicuticular wax morphology and lignin content in peel
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