+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Treatment of doxorubicin-resistant MCF7/Dx cells with nitric oxide causes histone glutathionylation and reversal of drug resistance



Treatment of doxorubicin-resistant MCF7/Dx cells with nitric oxide causes histone glutathionylation and reversal of drug resistance



Biochemical Journal 440(2): 175-183



Acquired drug resistance was found to be suppressed in the doxorubicin-resistant breast cancer cell line MCF7/Dx after pre-treatment with GSNO (nitrosoglutathione). The effect was accompanied by enhanced protein glutathionylation and accumulation of doxorubicin in the nucleus. Among the glutathionylated proteins, we identified three members of the histone family; this is, to our knowledge, the first time that histone glutathionylation has been reported. Formation of the potential NO donor dinitrosyl-diglutathionyl-iron complex, bound to GSTP1-1 (glutathione transferase P1-1), was observed in both MCF7/Dx cells and drug-sensitive MCF7 cells to a similar extent. In contrast, histone glutathionylation was found to be markedly increased in the resistant MCF7/Dx cells, which also showed a 14-fold higher amount of GSTP1-1 and increased glutathione concentration compared with MCF7 cells. These results suggest that the increased cytotoxic effect of combined doxorubicin and GSNO treatment involves the glutathionylation of histones through a mechanism that requires high glutathione levels and increased expression of GSTP1-1. Owing to the critical role of histones in the regulation of gene expression, the implication of this finding may go beyond the phenomenon of doxorubicin resistance.

(PDF emailed within 0-6 h: $19.90)

Accession: 056672784

Download citation: RISBibTeXText

PMID: 21834791

DOI: 10.1042/BJ20111333


Related references

Nitric oxide releasing acridone carboxamide derivatives as reverters of doxorubicin resistance in MCF7/Dx cancer cells. Bioorganic Chemistry 64: 51-58, 2017

Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance. Hematology 12(6): 511-517, 2007

Reversal of doxorubicin-resistance by Salvia miltiorrhiza ligustrazine in the SHG44/doxorubicin glioma drug-resistant cell line. Oncology Letters 14(4): 4708-4714, 2017

Verapamil reversal of doxorubicin resistance in multidrug-resistant human myeloma cells and association with drug accumulation and DNA damage. Cancer Research 48(22): 6365-6370, 1988

Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR. Zhonghua Zhong Liu Za Zhi 24(2): 129-132, 2002

Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux. Cancer Research 65(2): 516-525, 2005

Reversal effects of mifepristone on multidrug resistance(MDR) in drug-resistant breast cancer cell line MCF7/ADRin vitroandin vivo. Chinese Journal of Cancer Research 16(2): 93-98, 2004

Reversal of resistance to doxorubicin by CJZ3, a lomerizine amlodipine derivative,in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Zhongguo Yaolixue Tongbao 23(11): 1431-1436, 2007

Reversal of drug resistance by erythromycin: erythromycin increases the accumulation of actinomycin D and doxorubicin in multidrug-resistant cells. International Journal of Cancer 44(1): 149-154, 1989

Treatment of human breast cancer cells with nitric oxide mimetics prevents acquisition of hypoxia-induced resistance to doxorubicin. Proceedings of the American Association for Cancer Research Annual Meeting 42: 814-815, March, 2001

S9788 modulation of P-glycoprotein- and Multidrug-related protein-mediated multidrug resistance by Servier 9788 in doxorubicin-resistant MCF7 cells. Biochemical Pharmacology 56(4): 497-502, Aug 15, 1998

Metformin synergistically suppress tumor growth with doxorubicin and reverse drug resistance by inhibiting the expression and function of P-glycoprotein in MCF7/ADR cells and xenograft models. Oncotarget 9(2): 2158-2174, 2018

Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells. Chinese Journal of Natural Medicines 16(1): 20-28, 2018

Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect and reverses drug resistance in doxorubicin-resistant K562/DOX cells. Canadian Journal of Physiology and Pharmacology 83(3): 309-318, 2005

Methotrexate and mitoxantrone cross-resistance in selected drug-resistant MCF7 breast cancer cells. Proceedings of the American Association for Cancer Research Annual Meeting 40: 669-670, March, 1999