Tuberostemonine reverses multidrug resistance in chronic myelogenous leukemia cells K562/ADR

Abstract

Objective: To investigate the reversal effect of tuberostemonine on MDR in myelogenous leukemia cells K562/ADR.Methods: Human myelogenous leukemia cells K562 and their adriamycin-resistance cells K562/ADR were used. The growth curve of cells treated by tuberostemonine and the Non-toxic concentration of tuberostemonine were determined by MTT, Cell apoptosis was determined by MTT and flow cytometry. The expression of MDR1, Survivin and Livin was detected by RT-PCR. The activity of P-gp was detected by flow cytometry. Western blot was used to detect the expression of NF-κB and Survivin.Results: The effect of tuberostemonine on K562/ADR showed a dose-dependence, and 350μg/mL and 500μg/mL of tuberostemonine could inhibit the expression of MDR1 (P<0.05). While no function difference of P-gp was detected. With the increased concentration of tuberostemonine, the inhibitory effect were enhanced to the expression of NF-κB. Tuberostemonine combined with adriamycin could time-dependently inhibit the cell proliferation (P<0.05) and obviously promoted the cell apoptosis (P<0.05). Also the tuberostemonine could inhibit the expression of Survivin.Conclusion: There are no direct relations between tuberostemonine and P-gp, but tuberostemonine could reverse the multidrug resistance of K562/ADR via down-regulating the expression of Nf-κB and inhibiting th1e expression of Survivin.

Metabolic Reprogramming During Multidrug Resistance in Leukemias

“…No difference in Bcl-2 levels could be detected when Lucena-1 and FEPS were compared with their parental non-MDR cell line K562 ( 46 ). On the other hand, the inhibitor of apoptosis survivin is increased in these cells, similarly to what has been described in K562/ADR ( 73 ) and other MDR cell lines ( 74 , 75 ). Survivin suppresses cell death via caspase inhibition.…”

Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis

“…Overexpressing of ABC-transporters is recognized as the main cause of MDR, which is almost positive in all malignant tumor cells [7–9]. High level of ABC-transporters in leukemia cells may lead to increasing of drug efflux, decreasing intracellular drug concentration, thereby preventing the antiproliferation activity of chemotherapy drugs [10, 11]. Adriamycin (Adr) belongs to the anthracycline antibiotic family, displaying strong cytotoxicity and therefore generally being used as chemotherapeutic agents in clinical including leukemia [12].…”

Total Synthesis of Racemic (±)-Parvistemonine A

“…从结构上分析, 百部生物碱天然产物具有特征性 的吡咯并[1,2-α]氮杂环核(图 1) [1,2] . 由于其结构中具有 多样性的环骨架, 丰富的氢键供体和受体及丰富的 sp 3 杂化碳中心, 因而此类天然产物及其类似物表现出多种 生物活性, 如 Sigma 受体结合活性 [3] , 祛痰止咳 [4] , 抗花 叶病毒 [5] , 抗肿瘤 [6] , 逆转多药耐药抵抗等 [7,8] . 由于百 部生物碱具有广泛的生物活性, 因而其引起了广大合成 化学家的关注 [9] , 其中具有吡咯并 [1,2-α]氮杂环骨架的 stemoamide 已有 20 余种合成方法报道 [10] .…”