Study on curcumin analogues with high hydrolytic stability against multidrug-resistant tumor
10.7501/j.issn.0253-2670.2014.12.016
- Author:
Feng ZHANG
1
Author Information
1. College of Pharmacy, Henan University
- Publication Type:Journal Article
- Keywords:
Analogues;
Apoptosis;
Curcumin;
Hydrolytic stability;
Multidrug-resistance;
P-glycoprotein
- From:
Chinese Traditional and Herbal Drugs
2014;45(12):1736-1742
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect and mechanisms of a series of curcumin analogues with better hydrolytic stability on multidrug-resistant tumor. Methods: Human leukemia multi-drug resistant K562/A02 cells were incubated with curcumin and its analogues 1-19. MTT method was applied for screening the inhibition on the growth of K562/A02 cells; HPLC was used to detect the hydrolytic stability of curcumin and its analogues 3 and 4; The effects of curcumin and its analogues 3 and 4 on apoptosis, mitochondrial membrane potential (MMP), reaction oxygen species (ROS) content, and cell cycle distribution of K562/A02 cells were measured by flow cytometry; Spectrophotometric method was used to detect the caspase-3 activity; The expression of P-glycoprotein (P-gp) was assayed by Western blotting; Fluorometric method was applied to evaluating the intracellular Adriamycin accumulation of anti-tumor drug. Results: Analogues 3 and 4 exhibited the inhibitory effect on the growth of K562/A02 cells as similar as that of curcumin, but their hydrolytic stability was significantly higher than that of curcumin. Compared with the control group, curcumin and its analogues 3 and 4 could significantly promote apoptosis by reducing MMP and increasing caspase-3 activity of K562/A02 cells, but no obvious increase in intracellular ROS was found. In addition, the cell proportion of K562/A02 cells in G2/M and S phases was significantly reduced in the presence of curcumin and its analogues, while the hypodiploid increased. Besides, Western blotting indicated that the P-gp was significantly downregulated with an increase of intracellular anti-tumor drug accumulation. Conclusion: The analogues 3 and 4 of curcumin have the better hydrolytic stability than that of curcumin, while the anti-resistant tumor activity is maintained.
