Ligustrazine derivate DLJ14 reduces multidrug resistance of K562/A02 cells by modulating GSTπ activity

Yu-Ning Song, Xiu-Li Guo, Bei-Bei Zheng, Xin-Yong Liu, Xue Dong, Lu-Gang Yu, Yan-Na Cheng
Toxicology in Vitro: An International Journal Published in Association with BIBRA 2011, 25 (4): 937-43
Multidrug resistance (MDR) of tumor cells is a major obstacle in chemotherapeutic cancer treatment. Over-expression of glutathione S-transferase π (GSTπ) is one of the mechanisms contributing to MDR. In this study, we investigated the reversal of MDR by DLJ14, a ligustrazine derivate, in adriamycin (Adr) resistant human myelogenous leukemia (K562/A02) cells by modulating the expression of GSTπ and the activity of GST-related enzymes. In the MTT test, DLJ14 showed a weak inhibition on proliferation of both K562/A02 and K562 cells, while verapamil at the same concentration showed a much stronger inhibition. The sensitivity of K562/A02 cells to cytotoxic killing by Adr was enhanced by incubation with DLJ14 as a result of the increased intracellular accumulation of Adr. The accumulation of Adr induced by DLJ14 may due to down regulation of GST-related enzyme activity. Western blot analysis and RT-PCR showed that DLJ14 was able to inhibit the protein expression and mRNA expression of GSTπ in K562/A02 cells. Moreover, DLJ14 increased the expression of cellular c-Jun NH(2)-terminal kinase (JNK) in K562/A02 cells exposure to Adr. This is consistent with the inhibition of GSTπ. These results demonstrate that DLJ14 may be an attractive new agent for the chemosensitization of cancer cells.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"