Two series of territrem B analogues (6, 11) were designed and synthesized from jujubogenin 2. Compound 11c inhibited AChE with the ratio of 70% at 10-4 mol/L. Compounds 5a, 5b, 6a and 11b showed moderate cytotoxicit...Two series of territrem B analogues (6, 11) were designed and synthesized from jujubogenin 2. Compound 11c inhibited AChE with the ratio of 70% at 10-4 mol/L. Compounds 5a, 5b, 6a and 11b showed moderate cytotoxicity on cultured KB cells at 10-6 mol/L. Compounds 5c and 6b alleviated injury arising from oxygen-glucose deprivation (OGD).展开更多
Arsenic trioxide(ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resis...Arsenic trioxide(ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein(BCRP) inhibitor, or multidrug resistance protein 1(MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells.In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.展开更多
文摘Two series of territrem B analogues (6, 11) were designed and synthesized from jujubogenin 2. Compound 11c inhibited AChE with the ratio of 70% at 10-4 mol/L. Compounds 5a, 5b, 6a and 11b showed moderate cytotoxicity on cultured KB cells at 10-6 mol/L. Compounds 5c and 6b alleviated injury arising from oxygen-glucose deprivation (OGD).
基金supported by funds from NIH (No. 1R15CA143701)St. John's University Research Seed Grant (No. 579–1110-7002) to Zhe-Sheng Chen
文摘Arsenic trioxide(ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein(BCRP) inhibitor, or multidrug resistance protein 1(MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells.In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.
