HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

CXCL12/CXCR4 axis confers adriamycin resistance to human chronic myelogenous leukemia and oroxylin A improves the sensitivity of K562/ADM cells.

Abstract
This study was aimed at investigating the reversal effect of oroxylin A, a naturally bioactive monoflavonoid separated and purified from Scutellaria baicalensis Georgi, in human chronic myeloid leukemia (CML) and the underlying mechanisms. The results showed that CXCL12 could enhance the resistance of K562 cells to adriamycin (ADM) by increasing the expression of CXCR4, up-regulating the downstream PI3K/Akt pathway, and promoting translocation of NF-κB dimers into nucleus and subsequently decreasing the expression of apoptosis-related proteins in K562 cells. And we found that ADM resistance was partially reversed by CXCR4 siRNA transfection. Moreover, the sensitivity enhancement of oroxylin A was demonstrated by decreasing the expression of CXCR4 at both protein and mRNA levels, via PI3K/Akt/NF-κB pathway and triggering the apoptosis pathway in vitro. In addition, the in vivo study showed that oroxylin A increased apoptosis of leukemic cells with low systemic toxicity, and the mechanism was the same as in vitro study. In conclusion, all these results showed that oroxylin A improved the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.
AuthorsYu Wang, Hanchi Miao, Wei Li, Jing Yao, Yang Sun, Zhiyu Li, Li Zhao, Qinglong Guo
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 90 Issue 3 Pg. 212-25 (Aug 01 2014) ISSN: 1873-2968 [Electronic] England
PMID24858801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Flavonoids
  • Neoplasm Proteins
  • Receptors, CXCR4
  • 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
  • Doxorubicin
  • Phosphatidylinositol 3-Kinase
Topics
  • Animals
  • Antibiotics, Antineoplastic (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Chemokine CXCL12 (metabolism)
  • Doxorubicin (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Drug Resistance, Neoplasm (drug effects)
  • Female
  • Flavonoids (adverse effects, pharmacology, therapeutic use)
  • Humans
  • Leukemia, Myeloid, Chronic-Phase (drug therapy, metabolism)
  • Mice
  • Mice, Nude
  • Neoplasm Proteins (agonists, antagonists & inhibitors, genetics, metabolism)
  • Phosphatidylinositol 3-Kinase (chemistry, metabolism)
  • RNA Interference
  • Random Allocation
  • Receptors, CXCR4 (agonists, antagonists & inhibitors, genetics, metabolism)
  • Signal Transduction (drug effects)
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: