Multidrug resistance (MDR) of tumor cells is one of the major problems encountered during cancer chemotherapy. In this paper, we isolated eight triterpenoids from Poria cocos and evaluated their effects on reversing MDR of KBV200 cells. Eight triterpenoids increase significantly vincristine-induced cytotoxicity in drug-resistant KBV200 cells at the concentrations of 12.5 µg/mL and 25 µg/mL. Dehydrotumulosic acid showed the best reversal effect: it increased KBV200 apoptosis induced by vincristine and inhibited P-gp function through enhancing the accumulation and retention of fluorescent P-gp substrate rhodamine 123 in KBV200 cells but had no effect on P-gp expression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1055/s-0031-1298146 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dual inhibition of topoisomerase II and microtubule of podophyllotoxin derivative 5p overcomes cancer multidrug resistance.
Eur J Pharmacol
November 2024
The State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing, China. Electronic address:
Compound 5p is a 4β-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn't show the inhibitor of topoisomerase I.
View Article and Find Full Text PDFBI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo.
Cell Commun Signal
June 2024
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Background: Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date.
View Article and Find Full Text PDFPhenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus sp. 3A00409.
Molecules
April 2024
Fujian Provincial Key Laboratory of Pharmacology of Natural Medicine, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
Two new phenylspirodrimanes, stachybotrins K and L ( and ), together with eight known analogues (-), were isolated from deep-sea-derived sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis.
View Article and Find Full Text PDFDesign and Synthesis of Cyclolipopeptide Mimics of Dysoxylactam A and Evaluation of the Reversing Potencies against P-Glycoprotein-Mediated Multidrug Resistance.
J Med Chem
March 2024
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, , with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 μM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression.
View Article and Find Full Text PDFModular Biomimetic Strategy Enabled Discovery of Simplified Pseudo-Natural Macrocyclic P-Glycoprotein Inhibitors Capable of Overcoming Multidrug Resistance.
J Med Chem
February 2023
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Natural macrocycles have shown impressive activity to overcome P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). However, the total synthesis and structural modification of natural macrocycles are challenging, which would hamper the deeper investigations of their structure-activity relationship (SAR) and drug likeness. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring polysubstituted 1,3-diene, which efficiently inhibited P-gp and reversed MDR in cancer cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!