C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line

Nishanth, Reddy P.; Ramakrishna, Bellamkonda; Jyotsna, Radhika G.; Roy, Kunal; Reddy, Gorla V.; Reddy, Pratap K.; Reddanna, Pallu

doi:10.1016/j.ejphar.2010.09.011

Cited by 63 publications

(29 citation statements)

References 39 publications

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“…High rate of mortality, cirrhosis risk development, and HCC may occur in the long time unresponsiveness treatment of patients with HCV infection (31, 34-36). Increased MDR1 expression was reported in tumoral tissues of HCC when compared to the nontumoral samples (37).…”

Section: Discussionmentioning

confidence: 99%

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

et al. 2013

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BackgroundTo treat viral infection of chronic hepatitis C (CHC) is a main strategy to prevent progression of liver disease, and cancer. Some patients with CHC have failed to respond to the common antiviral therapy in different populations.ObjectivesIn the current study it was aimed to find out the possible role of multiple drug resistance gene1 (MDR1) in non-responder patients with CHC infection in Turkish population.Patients and MethodsPeripheral blood-EDTA samples were used for total genomic DNA isolation. In total of 55 patients with chronic hepatitis C and positive results for genotype 1 [31 male (56.4%), 24 female (43.6%) and mean age-min-max; 56.9 ± 9.66 (39-71)]; 19 responder (34.5%), 21 non responder (38.2%), and 15 recurrence (27.3%) were included in the presented results. Functional MDR1 gene was genotyped by multiplex PCR-based reverse-hybridization Strip Assay method, and some samples were confirmed by direct sequencing.ResultsOur results indicate that MDR1 gene polymorphism is strongly associated with non-responder patients and those with recurrent chronic hepatitis C during conventional drug therapy when compared to the responder patients. Homozygous of the TT genotype for MDR1 exon 26 polymorphism was at 2.0-fold higher risk of non-responder than patients with CC and CT.ConclusionsThe homozygous MDR1 3435TT genotype which encodes the xenobiotic transporter P-glycoprotein may be associated with a poor antiviral response in HCV chronicity during conventional therapy, and large-scale studies are needed to validate this association.

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Section: Discussionmentioning

confidence: 99%

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

et al. 2013

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“…S4C). It has recently been reported that DPI inhibits the expression of multidrug resistance-1 gene (MDR1) in hepatocellular carcinoma cells (33), which can alter drug pharmacodynamics. However, DPI did not altered MDR1 messenger levels in K562 cells (Supplementary Fig.…”

Section: Im/dpimentioning

confidence: 99%

NADPH Oxidases as Therapeutic Targets in Chronic Myelogenous Leukemia

Sánchez-Sánchez

Gutiérrez-Herrero

López-Ruano

et al. 2014

Clinical Cancer Research

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Purpose: Cancer cells show higher levels of reactive oxygen species (ROS) than normal cells and increasing intracellular ROS levels are becoming a recognized strategy against tumor cells. Thus, diminishing ROS levels could be also detrimental to cancer cells. We surmise that avoiding ROS generation would be a better option than quenching ROS with antioxidants. Chronic myelogenous leukemia (CML) is triggered by the expression of BCR-ABL kinase, whose activity leads to increased ROS production, partly through NADPH oxidases. Here, we assessed NADPH oxidases as therapeutic targets in CML.Experimental Design: We have analyzed the effect of different NADPH oxidase inhibitors, either alone or in combination with BCR-ABL inhibitors, in CML cells and in two different animal models for CML.Results: NADPH oxidase inhibition dramatically impaired the proliferation and viability of BCR-ABLexpressing cells due to the attenuation of BCR-ABL signaling and a pronounced cell-cycle arrest. Moreover, the combination of NADPH oxidase inhibitors with BCR-ABL inhibitors was highly synergistic. Two different animal models underscore the effectiveness of NADPH oxidase inhibitors and their combination with BCR-ABL inhibitors for CML targeting in vivo.Conclusion: Our results offer further therapeutic opportunities for CML, by targeting NADPH oxidases. In the future, it would be worthwhile conducting further experiments to ascertain the feasibility of translating such therapies to clinical practice. Clin Cancer Res; 20(15); 4014-25. Ó2014 AACR.

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“…Previous studies using various tumor cell lines have shown that ABCB1 expression can be regulated through the MAPK pathway 23,24 , involvement of the transcription factor AP-1 25 or reactive oxygen species 26 , and/or NF-κB signaling and CRE transcriptional activity 27 . As the induction of BRAF V600E causes MEK-ERK activation in our model, we first examined this pathway using the BRAF V600E inhibitor vemurafenib and the MEK inhibitor CI-1040.…”

Section: Resultsmentioning

confidence: 99%

BRAFV600E induces ABCB1/P-glycoprotein expression and drug resistance in B-cells via AP-1 activation

et al. 2015

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A subset of patients with chronic lymphocytic leukemia (CLL) and nearly all patients with classic hairy cell leukemia (HCL) harbor somatic BRAF activating mutations. However, the pathological role of activated BRAF in B-cell leukemia development and progression remains unclear. In addition, although HCL patients respond well to the BRAFV600E inhibitor vemurafenib, relapses are being observed, suggesting the development of drug resistance in patients with this mutation. To investigate the biological role of BRAFV600E in B-cell leukemia, we generated a CLL-like B-cell line, OSUCLL, with doxycycline-inducible BRAFV600E expression. Microarray and real-time PCR analysis showed that ABCB1 mRNA is upregulated in these cells, and P-glycoprotein (P-gp) expression as well as function were confirmed by immunoblot and rhodamine exclusion assays. Additionally, pharmacological inhibition of BRAFV600E and MEK alleviated the BRAFV600E-induced ABCB1/P-gp expression. ABCB1 reporter assays and gel shift assays demonstrated that AP-1 activity is crucial in this mechanism. This study therefore uncovers a pathological role for BRAFV600E in B-cell leukemia, and provides further evidence that combination strategies with inhibitors of BRAFV600E and MEK can be used to delay disease progression and occurrence of resistance.

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C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line

Cited by 63 publications

References 39 publications

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

NADPH Oxidases as Therapeutic Targets in Chronic Myelogenous Leukemia

BRAFV600E induces ABCB1/P-glycoprotein expression and drug resistance in B-cells via AP-1 activation

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