Combined treatment of P-gp-positive L1210/VCR cells by verapamil and all-trans retinoic acid induces down-regulation of P-glycoprotein expression and transport activity

Sulová, Zdena; Macejova, Dana; Šereš, Mário; Sedlák, J; Brtko, Július; Breier, Albert

doi:10.1016/j.tiv.2007.08.011

Cited by 19 publications

(24 citation statements)

References 32 publications

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“…Celecoxib had been proven to down-regulate the ABC transporters P-glycoprotein (P-gp) and to enhance the accumulation of chemotherapy agents in human colon cancer Caco-2 cell line, which helped overcome multidrug resistance (MDR) [21]. It had also been proven that ATRA was not a P-gp-transportable substance [22]. Thus, the increase in retinoid sensitivity induced by celecoxib could not be attributed to the celecoxib-induced inhibition of P-gp.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Liu

Zheng

et al. 2010

Cellular and Molecular Biology Letters

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Abstract:Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE 2 production was measured with the ELISA assay. The expression of RARβ was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE 2 did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARβ in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE 2 did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARβ and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

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Section: Discussionmentioning

confidence: 99%

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Liu

Zheng

et al. 2010

Cellular and Molecular Biology Letters

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“…These two receptors could be classified as adopted orphan receptors with a specific ligands (including VCR Breier et al 2013b) identified in recent years (Shi 2007) and are dimerization partners of retinoid X receptors (Saeki et al 2010) with known ligand 9-cis retinoic acid (Brtko and Thalhamer 2003;Brtko and Dvorak 2011). Interestingly, the role of regulatory pathway of nuclear receptors for retinoids in development of P-gp-mediated MDR could take part (Sulova et al 2008(Sulova et al , 2012Breier et al 2014). Nestin was assumed to be transcriptionally controlled by the orphan receptor Nurr1 (Kappen and Yaworsky 2003), which the ligands are currently unknown (Shi 2007).…”

Section: Mdr1→mentioning

confidence: 99%

Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript

Imrichova¹,

Coculova²,

Messingerová³

et al. 2014

gpb

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Abstract.Nestin is a class 6 filament protein typically expressed in neural stem/progenitor cells. However, nestin expression has been observed in other tissues during mammalian embryogenesis. In human neural stem/progenitor cells, coexpression of nestin and P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family) was detected. P-gp-mediated drug efflux is the most common molecular cause of multidrug resistance in neoplastic cells. Nestin expression has also been detected in various human solid tumours as well as in the corresponding established cell lines. Interestingly, expression of nestin in different leukemia cells has been recently reported. Here, we show that expression of P-gp is associated with the simultaneous expression of nestin in acute myeloid leukemia cell lines (MOLM-13 and SKM-1) under the selective pressure of vincristine, a substance that may induce P-gp expression in neoplastic cells.

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“…274 2.5. Determination of the P-gp, NF-kB, p53, Bcl-2, Bax and GAPDH 275 protein levels in sensitive and resistant SKM-1 and MOLM-Examination of P-gp function by the calcein/AM assay in sensitive 307and Vcr-resistant variants of SKM-1 and MOLM-13 cells 308 P-gp transport activity was measured using a previously 309 described calcein retention assay(Sulova et al, 2008). To remove310 AzaC after cultivation, cells were centrifuged (500g) and washed 311 three times with PBS containing 0.2% BSA.…”

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confidence: 99%

Acute myeloid leukemia cells MOLM-13 and SKM-1 established for resistance by azacytidine are crossresistant to P-glycoprotein substrates

Messingerová

Imrichova

Kavcová

et al. 2015

Toxicology in Vitro

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Combined treatment of P-gp-positive L1210/VCR cells by verapamil and all-trans retinoic acid induces down-regulation of P-glycoprotein expression and transport activity

Cited by 19 publications

References 32 publications

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript

Acute myeloid leukemia cells MOLM-13 and SKM-1 established for resistance by azacytidine are crossresistant to P-glycoprotein substrates

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Combined treatment of P-gp-positive L1210/VCR cells by verapamil and all-trans retinoic acid induces down-regulation of P-glycoprotein expression and transport activity

Cited by 19 publications

References 32 publications

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript

Acute myeloid leukemia cells MOLM-13 and SKM-1 established for resistance by azacytidine are crossresistant to P-glycoprotein substrates

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Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript