Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib

Ferrario, Angela; Lim, Sophia; Xu, Frank F.; Luna, Marian; Gaffney, Kevin J.; Petasis, Nicos A.; Schönthal, Axel H.; Gomer, Charles J.

doi:10.1016/j.canlet.2011.01.023

Cited by 23 publications

(20 citation statements)

References 46 publications

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“…Similarly, the 293T cell line (human embryonic kidney) was cultured in Dulbecco's modified Eagle's medium (Sigma, Bornem, Belgium) supplemented with 10% (v/v) fetal calf serum (Brunschwig, Basel, Switzerland) and 1% (v/v) of penicillin/ streptomycin from BioWhittaker. Peripheral blood mononuclear cells from healthy adult human donors were isolated by standard density separation method using Ficoll-Hypaque from GE Healthcare (Rosendaal, The Netherlands) as previously described (Ferrario et al, 2011). Purified peripheral blood mononuclear cells (PBMCs) were washed twice with phosphate-buffered saline (PBS)-1X and resuspended in RPMI 1640 supplemented with 10% fetal bovine serum and 1% antibioticantimycotic solution at a cell density of 2.0 Â 10 6 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

“…In this paper, we demonstrated that DMC possess stronger antitumor properties than celecoxib. Some studies demonstrated synergistic or additive effect between DMC and chemotherapy (Kardosh et al, 2008) or photodynamic therapy (Ferrario et al, 2011). In U937 cells, we already published that a combination of celecoxib or DMC with etoposide (VP16) does not generate any beneficial effects (Cerella et al, 2011b).…”

Section: Dmc Induces Apoptosis and Cell Cycle Alterations In Leukemiamentioning

confidence: 99%

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2,5-Dimethyl-Celecoxib Inhibits Cell Cycle Progression and Induces Apoptosis in Human Leukemia Cells

Sobolewski

Rhim

Legrand

et al. 2015

J Pharmacol Exp Ther

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Cyclooxygenase-2 (COX-2) is an essential regulator of cancer promotion and progression. Extensive efforts to target this enzyme have been developed to reduce growth of cancer cells for chemopreventive and therapeutic reasons. In this context, cyclooxygenase-2 inhibitors present interesting antitumor effects. However, inhibition of COX-2 by anti-COX-2 compounds such as celecoxib was recently associated with detrimental cardiovascular side effects limiting their clinical use. As many anticancer effects of celecoxib are COX-2 independent, analogs such as 2,5-dimethyl-celecoxib (DMC), which lacks COX-2-inhibitory activity, represent a promising alternative strategy. In this study, we investigated the effect of this molecule on growth of hematologic cancer cell lines (U937, Jurkat, Hel, Raji, and K562). We found that this molecule is able to reduce the growth and induces apoptosis more efficiently than celecoxib in all the leukemic cell lines tested. Cell death was associated with downregulation of Mcl-1 protein expression. We also found that DMC induces endoplasmic reticulum stress, which is associated with a decreased of GRP78 protein expression and an alteration of cell cycle progression at the G1/S transition in U937 cells. Accordingly, typical downregulation of c-Myc and cyclin D1 and an upregulation of p27 were observed. Interestingly, for shorter time points, an alteration of mitotic progression, associated with the downregulation of survivin protein expression was observed. Altogether, our data provide new evidence about the mode of action of this compound on hematologic malignancies.

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Section: Methodsmentioning

confidence: 99%

Section: Dmc Induces Apoptosis and Cell Cycle Alterations In Leukemiamentioning

confidence: 99%

2,5-Dimethyl-Celecoxib Inhibits Cell Cycle Progression and Induces Apoptosis in Human Leukemia Cells

Sobolewski

Rhim

Legrand

et al. 2015

J Pharmacol Exp Ther

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“…Combined strategies have been introduced for cancer treatments, including PDT with tumor suppressors, 10, 11 inhibitors, 12 and anti-angiogenic drugs. 2 Another way to enhance PDT efficacy involves an increase in PS delivery and specificity through conjugation to tumor-targeting molecules.…”

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confidence: 99%

Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer

et al. 2014

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Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm2, respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24 h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone).

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“…10 Hence, research interests are on the rise to improve the PDT effectiveness and expand its applications. 11 12 One such interest is the development of suitable drug delivery systems that can reduce the photosensitizer's hydrophobicity to enhance tumour selectivity. The delivery agents mainly include microcapsules, 13 liposomes, 14 micelles 15 and nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol-Modified Gelatin/Polylactic Acid Nanoparticles for Enhanced Photodynamic Efficacy of a Hypocrellin Derivative <I>In Vitro</I>

Babu¹,

Periasamy²,

Gunasekaran³

et al. 2013

j biomed nanotechnol

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The present study focused on the development of a novel biodegradable nanoparticle system based on polyethyleneglycol-modified gelatin (PEG-GEL) and polylactic acid (PLA) biopolymers for improving the photodynamic efficacy of cyclohexane-1,2-diamino hypocrellin B (CHA2HB), a potent photodynamic therapeutic (PDT) agent. The CHA2HB-loaded PEG-GEL/PLA nanoparticles showed near-spherical morphology with an average size of 190 nm at a PLA to PEG-GEL ratio of 1:3. The drug loading was sufficient enough to produce potentially toxic reactive oxygen species (ROS) needed for photodynamic therapy (PDT). Slow and controlled drug release was observed in normal conditions, whereas enzyme assistance resulted in a relatively fast release due to partial disintegration of CHA2HB-loaded PEG-GEL/PLA nanoparticles. In vitro experiments indicated that CHA2HB-loaded PEG-GEL-PLA nanoparticles are efficiently taken up by cancer cells such as human breast adenocarcinoma (MCF-7), human gastric sarcoma (AGS) and mice specific Dalton's lymphoma (DLA) in a time dependent manner. Further, CHA2HB-loaded PEG-GEL/PLA nanoparticles evoked superior phototoxicity compared to free-CHA2HB towards all the three cell lines investigated. Interestingly, PDT effectiveness was different for the different cell type studied. CHA2HB-loaded PEG-GEL/PLA nanoparticles induced both apoptotic and necrotic cell death as a result of photoirradiation. Thus, our data suggest that PEG-GEL/PLA nanoparticles are highly effective in delivery and phototoxic enhancement of CHA2HB against model cancer cells in vitro.

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Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib

Cited by 23 publications

References 46 publications

2,5-Dimethyl-Celecoxib Inhibits Cell Cycle Progression and Induces Apoptosis in Human Leukemia Cells

2,5-Dimethyl-Celecoxib Inhibits Cell Cycle Progression and Induces Apoptosis in Human Leukemia Cells

Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer

Polyethylene Glycol-Modified Gelatin/Polylactic Acid Nanoparticles for Enhanced Photodynamic Efficacy of a Hypocrellin Derivative <I>In Vitro</I>

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