Celecoxib enhances sensitivity to chemotherapy drugs of T‑cell lymphoma

Abstract

Abstract. Celecoxib is a newly-identified nonsteroidal anti-inflammatory drug, which has been used to treat fever in clinical practice. Celecoxib has been demonstrated to suppress the viability of various human tumor cells. However, the effect of celecoxib on response of T-cell lymphoma to chemotherapy agents remains unclear. The aim of the present study was to investigate the effect of celecoxib on chemosensitivity of human T-cell lymphoma, and to address the underlying mechanism of action. The cytotoxicity of CDDP, epirubicin and VCR on Jurkat and Hut-78 cells treated with celecoxib was assessed by MTT assay, and the half-maximal inhibitory concentration (IC 50 ) value was calculated by Origin 75 software. The effect of celecoxib on apoptosis and intracellular concentration of Rhodamine-123 in Jurkat and Hut-78 cells was analyzed by flow cytometry. The expression of transcription factor p65 (p65), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) at mRNA and protein levels were detected by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Proliferation suppression rates and apoptosis levels were significantly increased in Jurkat and Hut-78 cells combined with celecoxib compared with those without celecoxib, when treated with CDDP, epirubicin and VCR. The IC 50 values of the chemotherapy agents were lower in Jurkat and Hut-78 cells treated with celecoxib compared with those that were not.The apoptosis level, expression of Bax and the intracellular concentration of Rhodamine-123 were increased, whereas the expression of p65, Bcl-2, MDR1 and MRP1 were decreased, in celecoxib-treated Jurkat and Hut-78 cells compared with those without celecoxib treatment. These results indicated that celecoxib may enhance the sensitivity of T-cell lymphoma to chemotherapy drugs by inhibiting the expression of multidrug resistance (MDR)-associated proteins via downregulating the activity of the nuclear factor-κB signaling pathway, suggesting that celecoxib may improve the curative effect of chemotherapy drugs in T-cell lymphoma.

Preferential Binding of Epirubicin Hydrochloride with Single Nucleotide Mismatched DNA and Subsequent Sequestration by a Mixed Micelle

“…In recent years, research has been directed toward the identification and design of site- and sequence-specific DNA-binding small-molecule drugs to make the nucleic acids a new drug discovery target. Most of the anticancer drugs bind to DNA in a more sequence-specific manner through various kinds of noncovalent interaction modes such as external binding with a phosphate backbone, groove binding, and intercalation between base pairs. − These types of noncovalent binding modes are reversible and typically preferred over covalent binding, keeping the toxic side effects and drug metabolism in mind. − Anthracycline drug epirubicin hydrochloride (EPR, Scheme a) is one of the most imperative anticancer drugs − used in the treatment of leukemia, lymphoma, and sarcoma and is reported to be less toxic compared to its parent compound doxorubicin. , In a cancer cell, it localizes inside the nucleus by forming a complex with DNA through an intercalation mode of binding. , This complex prevents topoisomerase II by interfering with protein synthesis, and hence the subsequent DNA replication stops . However, an in-depth elucidation of the sequence-selective binding interaction of EPR with DNA through a systematic study and its binding aspects toward single nucleotide mismatched base pairs containing DNA, which is overexpressed in cancer cells, is not well understood.…”

Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

“…P-gp plays an important role in determining the concentration of substrates inside the cells; P-gp located in the plasma membrane directly effluxes cytotoxic drugs from cells and, therefore, reduces their concentration [37]. It had been previously shown by others studies that chemotherapeutics or P-glycoprotein inhibitors affected P-gp expression levels in cancer cells and that this can be a cause of re-sensitization of MDR cells [43,44]. We evaluated the effects of Achillin on P-gp levels using immunofluorescence analysis and found that cancer resistant cells exposed to Achillin result in decrease in P-gp levels Figure 9.…”

Biological effects of formulation containing curcuminoids and Bidens Pilosa L. in oral carcinoma cell line

“…Similar to our findings, Alcazar et al 19 demonstrated that treating T lymphocytes with the chemical camptothecin for 3 h promoted the hyperpolarization of the mitochondrial membrane followed by the release of cytochrome c in the cellular cytosol. Recently, Ma et al 20 showed that treating T-cell lymphomas with celecoxib promoted an increased expression of Bax and rhodamine 123 accumulation by the tumor cells, as well as an induction of tumor apoptosis.…”