Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2

Abstract

Here, we investigated the role of zinc ribbon domaincontaining 1 (ZNRD1) in multidrug resistance (MDR) of leukemia cells and the possible underlying mechanisms. ZNRD1 was found overexpressed in the vincristineinduced MDR leukemia cell HL-60/vincristine moreso than its parental cell HL-60. Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin. ZNRD1 could significantly upregulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells. In addition, inhibition of ZNRD1 expression by RNA interference or P-gp inhibitor could partially reverse ZNRD1-mediated MDR. The further study of the biological functions of ZNRD1 may be helpful for understanding the mechanisms of MDR of leukemia and developing possible strategies to treat leukemia. [Mol Cancer Ther 2005;4(12):1936 -42]

miR-126 Suppresses the Proliferation of Cervical Cancer Cells and Alters Cell Sensitivity to the Chemotherapeutic Drug Bleomycin

“…Each sample was evaluated in 3 replicates. Survival rates (SR) were calculated using the MTT assay as previously described ( (Hong et al, 2005). Briefly, 20 μL of 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT; 5 mg/mL; Sigma, St Louis, USA) was added into each well at 0, 24, 48, 72, and 96 h after transfection.…”

ZNRD1 (Zinc Ribbon Domain–Containing 1) Is a Host Cellular Factor That Influences HIV‐1 Replication and Disease Progression

“…ZNRD1 encodes a protein consisting of 2 zinc ribbon domains [14]. The C-terminal domain is well conserved in many organisms as a transcription-associated motif [15].…”

A comparative study of cytotoxic, membrane and DNA damaging effects of Origanum majorana’s essential oil and its oxygenated monoterpene component linalool on parental and epirubicin-resistant H1299 cells

“…This will be the reason for essential oil's and linalool's less cytotoxicity on drug-resistant cells than parental cells. Extrusion of the drug by cell membrane pumps, increased DNA damage repair, redistribution of intracellular accumulation of drugs, modification of drug target molecules, suppression of druginduced apoptosis, up-regulation of lipids and other biochemical changes will also be the others reasons (Hong et al 2005). Ramadan et al (2012) reported that both sweet marjoram leaf powder and marjoram leaf aqueous extract significantly alleviated most side effects and toxicity of cyclophosphamide (one of the most popular alkylating anticancer drugs) treated rats (non-tumour bearing) including the increase in chromosomal aberrations of bone marrow cells and serum MDA level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells.…”