Enhancement of fludarabine sensitivity by all-trans-retinoic acid in chronic lymphocytic leukemia cells

Fernández-Calotti, Paula; López‐Guerra, Mònica; Colomer, Dolors; Pastor‐Anglada, Marçal

doi:10.3324/haematol.2011.051557

Cited by 17 publications

(18 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this sense, we have shown that hCNT3 trafficking to the plasma membrane can be induced in the CLL‐derived cell line MEC1, by all‐trans retinoic acid through a TGF‐β1‐mediated mechanism that requires ERK 1/2 and RhoA activation and cytoskeleton integrity (13). This effect can also be reproduced in primary CLL cells in cases of poor ex vivo response to fludarabine treatment (31).…”

Section: Discussionmentioning

confidence: 98%

“…In absorptive epithelia, apical localization of hCNT3 is crucial to determining the vectorial flux of many antiviral and anticancer nucleosides tested so far (5), thus being a major candidate for modulating drug bioavailability and pharmacokinetics. However, in some pathologic conditions such as cancer, hCNTs seem to be down‐regulated (29–31). In this regard, it has been reported that low plasma membrane expression of hCNT3 may be related to the poor response to treatment of chronic lymphocytic leukemia (CLL) cells (32).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

et al. 2015

View full text Add to dashboard Cite

The intracellular N-terminal domain of the nucleoside and drug transporter human concentrative nucleoside transporter (hCNT)3 was used as bait in a glutathione S-transferase pull-down approach, to identify hCNT3 protein partners, using human colon homogenates as a prey source. Galectin (Gal)-4 was identified as a potential hCNT3 partner in the colon. The biochemical validation of the Gal-4-hCNT3 interaction was verified by targeted pull-down assays and coimmunoprecipitation experiments in HT-29 cells, which endogenously express hCNT3 and Gal-4. Furthermore, Gal-4 was shown to colocalize with hCNT3 in HT-29 cells. The biologic significance of this interaction was obtained from experiments in which Gal-4 was knocked down, showing that this protein is a regulator of hCNT3 trafficking and retention at the cell membrane, reducing its plasma membrane location by 70%. Conversely, the addition of Gal-4 increased hCNT3 location at the plasma membrane by 77%, thereby demonstrating that this lectin modulates hCNT3 function in colonic cells. The integrity of this partnership may be clinically relevant, because hCNT3 may be responsible for the translocation of thiopurines, such as 6-mercaptopurine, a front-line treatment in inflammatory bowel disease. The expression of Gal-4 and hCNT3 proteins is not impaired in inflamed colon from patients with Crohn's disease, thereby anticipating the integrity of this system for drug targeting.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Pharmacology [5] and lung cancer [6] as auxiliary medication. Retinoic acid participates in renal development [7,8], and dietary deficiency during pregnancy leads to less number of nephrons at birth [9].…”

Section: Fundamental and Clinicalmentioning

confidence: 99%

“…Many substances have been studied to try to find an appropriate therapeutic tool for preventing or treating kidney pathologies. Among them, the retinoids have been proposed as possible candidates in the literature: retinoids have proved to be useful in human leukemia and lung cancer as auxiliary medication. Retinoic acid participates in renal development , and dietary deficiency during pregnancy leads to less number of nephrons at birth .…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid improves recovery after nephrectomy and decreases renal TGF‐β1 expression. Gender‐related effects

Delgadillo‐Guzmán

Barbier

Sierra

et al. 2012

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

End-stage renal disease is a cause for death worldwide. Renal transplant is a therapeutic alternative, restricted by the scant number of donors. Function of the donor kidney is under risk of adverse circumstances such as fibrosis, where profibrotic effect of transforming growth factor beta 1 (TGF-β1) plays a key role. Efforts to diminish risks of damage in the remnant kidney of the donor are required. Vitamin A represents one alternative. It has beneficial effects on some nephropathies, mainly those related to oxidative stress. It also participates in normal intrauterine renal development. We studied the effect of all-trans retinoic acid (ATRA), active form of vitamin A, on postnephrectomy compensatory growth, in male or female rats. Compensatory growth and renal function were evaluated on four experimental groups: Control without treatment (CTL), ATRA-treated intact rats (CTL + RA), nephrectomized rats (NFX), and ATRA-treated nephrectomized rats (NFX + RA). We evaluated glomerular function (inulin clearance), tubular function (fractional excretions of sodium and potassium), and urinary flow. Renal mass was also estimated. In ATRA-treated animals, compensatory growth was higher than in nephrectomized rats without treatment. Hyperfiltration after nephrectomy was less intense in ATRA-treated female than in male rats. In tubular functions, effect of ATRA was more evident in female than in male rats. Glomerular expression of TGF-β1 was lower in ATRA-treated animals than in controls. ATRA reduced intensity and duration of compensatory changes after nephrectomy, improving recovery.

show abstract

“…Late-stage B-CLL is frequently treated with several different regiments including chemotherapeutic combinations composed of [i] fludarabine and Rituximab (FR); [ii] fludarabine and cyclophosphamide (FC); [iii] fludarabine, cyclophosphamide, and Rituximab (FCR); and [iv] cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). The combination of fludarabine and all-trans retinoic acid has enhanced levels of effectiveness against B-CLL [7] as does fludarabine with alkylating agents (cyclophosphamide) which promotes higher response rates and longer progression-free survival.…”

Section: Introductionmentioning

confidence: 99%

Fludarabine- (C2-methylhydroxyphosphoramide)- [anti-IGF-1R]: Synthesis and Selectively Targeted Anti-Neoplastic Cytotoxicity against Pulmonary Adenocarcinoma (A549)

Coyne

Narayanan

2015

J Pharm Drug Deliv Res

View full text Add to dashboard Cite

Introduction Many if not most conventional small molecular weight chemotherapeutics are highly potent against many forms of neoplastic disease. Unfortunately, majority of an administered dose unintentionally diffuses passively into normal tissues and healthy organ systems following intravenous administration. One strategy for both increasing potency and reducing dose-limited sequela is the selective “targeted” delivery of conventional chemotherapeutic agents. Materials and Methods The fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] was synthesized by initially reacting fludarabine with a carbodiimide to form a fludarabine carbodiimide phosphate ester intermediate that was subsequently reacted with imidazole to create an amine-reactive fludarabine- (C2-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with the amine-reactive fludarabine- (C2-phosphorylimidazolide) intermediate resulting in the synthesis of covalent fludarabine-(C2-methylhydroxyphosphoramide)- [anti-IGF-1R] immunochemotherapeutic. Residual fludarabine and un-reacted reagents were removed by serial microfiltration (MWCO 10,000) and monitored by analytical-scale HP-TLC. Retained IGF-1R binding-avidity of fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] was established by cell-ELISA using pulmonary adenocarcinoma cell (A549) which over-expresses IGF-1R and EGFR. Anti-neoplastic cytotoxic potency of fludarabine-(C2-methylhydroxyphosphoramide)-[anti- IGF-1R] was determined against pulmonary adenocarcinoma (A549) using an MTT-based vitality stain methodology. Results The fludarabine molar-incorporation-index for fludarabine- (C2-methylhydroxyphosphoramide)-[anti-IGF-R1] was 3.67:1 while non-covalently bound fludarabine was not detected by analytical scale HP-TLC following serial micro-filtration. Size-separation fludarabine-(C2-methylhydroxyphosphoramide)-[anti- IGF-1R] by SDS-PAGE with chemo luminescent autoradiography detected only a single 150-kDa band. Cell-ELISA of fludarabine- (C2-methylhydroxyphosphoramide)-[anti-IGF-1R] measuring total immunoglobulin bound to exterior surface membranes of pulmonary adenocarcinoma (A549) increased with elevations in immunoglobulin-equivalent concentrations of the covalent fludarabine immunochemotherapeutic. Between the fludarabine-equivalent concentrations of 10−10 M and 10−5 M both fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] and fludarabine had ex-vivo anti-neoplastic cytotoxic potency levels that increased rapidly between the fludarabine-equivalent concentrations of 10−6 M and 10−5 M where cancer cell death percentages increased from 24.4% to a maximum of 94.7% respectively. Conclusion The molecular design and organic chemistry reaction schemes were developed for synthesizing fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] which possessed both properties of selective “targeted” delivery and anti-neoplastic cytotoxic potency equivalent to fludarabine chemotherapeutic.

show abstract

Enhancement of fludarabine sensitivity by all-trans-retinoic acid in chronic lymphocytic leukemia cells

Cited by 17 publications

References 44 publications

Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

Retinoic acid improves recovery after nephrectomy and decreases renal TGF‐β1 expression. Gender‐related effects

Fludarabine- (C2-methylhydroxyphosphoramide)- [anti-IGF-1R]: Synthesis and Selectively Targeted Anti-Neoplastic Cytotoxicity against Pulmonary Adenocarcinoma (A549)

Contact Info

Product

Resources

About