The Effect of Indomethacin on Paclitaxel Sensitivity and Apoptosis in Oral Squamous Carcinoma Cells&lt;subtitle&gt;The Role of Nuclear Factor–κB Inhibition&lt;/subtitle&gt;

Caicedo-Granados, Emiro; Wuertz, Beverly R.; Marker, Paul H.; Lee, Gi Soo; Ondrey, Frank G.

doi:10.1001/archoto.2011.131

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…Paclitaxel induces apoptosis through the activation of JNK [31], while the phosphorylation of ERK [32,33], Bad [34] and IκBα [35] results in paclitaxel resistance. Our study revealed that treatment with paclitaxel increased the phosphorylation levels of JNK, IκBα, Bad and ERK, which was in line with previous studies.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel

Feng

Li²,

Chen³

et al. 2012

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This study aimed to investigate the effects of RhoGDIα knockdown on apoptosis and the chemosensitivity of lung cancer cells to paclitaxel. The signaling proteins involved were also assessed. RhoGDIα expression was assessed by RT-PCR, Western blotting and immunohistochemistry. Apoptosis was determined by flow cytometric assessment, and cell viability was measured with the MTT assay. Phosphorylation levels of signaling proteins, ERK, JNK, Akt, Bad and IκBα were tested by Western blotting and immunohistochemistry. Positivity for RhoGDIα in lung cancer tissues was significantly higher than in paracancerous tissues. Downregulation of RhoGDIα was associated with significantly increased apoptosis and repressed cell viability. This effect could be due to the consequent upregulation of p-JNK, as well as decreased levels of p-ERK, p-Bad and p-IκBα. Knockdown of RhoGDIα strengthened the effect on apoptosis and inhibition of cell viability induced by paclitaxel treatment. This chemosensitization effect could be a result of the intensification of pro-apoptotic JNK activation, and repression of anti-apoptotic p-ERK, p-Bad and p-IκBα expression stimulated by paclitaxel. In summary, our study indicated that RhoGDIα could be a promising therapeutic target, and the combination of RhoGDIα siRNA and paclitaxel might be a valuable potential therapy for lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel

Feng

Li²,

Chen³

et al. 2012

neo

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“…Evidence exists showing that SLPI inhibits NF-κB[32], [33], although this has not been demonstrated in models of oral cancer. Given this evidence, we sought to investigate whether or not SLPI decreases NF-κB activity in MSK-Leuk1 cells, using a luciferase-based reporter assay[34]. We treated the transfected MSK Leuk1 cells with two different concentrations of pure SLPI peptide (20 ug/mL and 40 ug/mL), and measured NF-κB at different times after treatment ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Oral Brush Biopsies Identifies Secretory Leukocyte Protease Inhibitor as a Promising, Mechanism-Based Oral Cancer Biomarker

et al. 2014

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A decrease in the almost fifty percent mortality rate from oral cancer is needed urgently. Improvements in early diagnosis and more effective preventive treatments could affect such a decrease. Towards this end, we undertook for the first time an in-depth mass spectrometry-based quantitative shotgun proteomics study of non-invasively collected oral brush biopsies. Proteins isolated from brush biopsies from healthy normal tissue, oral premalignant lesion tissue (OPMLs), oral squamous cell carcinoma (OSCC) and matched control tissue were compared. In replicated proteomic datasets, the secretory leukocyte protease inhibitor (SLPI) protein stood out based on its decrease in abundance in both OPML and OSCC lesion tissues compared to healthy normal tissue. Western blotting in additional brushed biopsy samples confirmed a trend of gradual decreasing SLPI abundance between healthy normal and OPML tissue, with a larger decrease in OSCC lesion tissue. A similar SLPI decrease was observed in-vitro comparing model OPML and OSCC cell lines. In addition, exfoliated oral cells in patients’ whole saliva showed a loss of SLPI correlated with oral cancer progression. These results, combined with proteomics data indicating a decrease in SLPI in matched healthy control tissue from OSCC patients compared to tissue from healthy normal tissue, suggested a systemic decrease of SLPI in oral cells correlated with oral cancer development. Finally, in-vitro experiments showed that treatment with SLPI significantly decreased NF-kB activity in an OPML cell line. The findings indicate anti-inflammatory activity in OPML, supporting a mechanistic role of SLPI in OSCC progression and suggesting its potential for preventative treatment of at-risk oral lesions. Collectively, our results show for the first time the potential for SLPI as a mechanism-based, non-invasive biomarker of oral cancer progression with potential in preventive treatment.

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“…Besides, ROS also plays an important role in the ATO-induced apoptosis and cell death [28]. Consistent with this hypothesis, accumulating evidence indicates that L-buthionine-sulfoximine (BSO), a drug that depletes intracellular glutathione (GSH) and generates ROS, can sensitize the lung cancerous cells to ATO-induced cell death [24, 42, 44–46]. Moreover, ROS can activate ERK1/2 pathway [47] as well as p38 kinase [47, 48].…”

Section: Discussionmentioning

confidence: 98%

“…It has been shown that indomethacin induces apoptosis in vivo [38] and in vitro in some cancerous cells including lung [7, 8], colon [39, 40], and leukemia [41]. In this report, production of ROS has been mentioned as the main mechanism of apoptotic effect [42, 43]. Besides, ROS also plays an important role in the ATO-induced apoptosis and cell death [28].…”

Section: Discussionmentioning

confidence: 99%

Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

Mandegary

Torshabi

Seyedabadi

et al. 2013

BioMed Research International

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Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationale for combination therapy in successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX) inhibitors with arsenic trioxide (ATO) might be a possible treatment option. Methods. Cytotoxicity of ATO, dexamethasone (Dex), celecoxib (Cel), and Indomethacin (Indo) individually or in combination was determined at 24, 48, and 72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations. Results. The IC50s of ATO and Indo were 68.7 μmol/L and 396.5 μmol/L, respectively. Treatment of cells with combinations of clinically relevant concentrations of ATO and Indo resulted in greater growth inhibition and apoptosis induction than did either agent alone. Caspase-3 activity was considerably high in the presence of ATO and Indo but showed no difference in single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in the concurrent presence of both drugs. Conclusions. Combination therapy with ATO and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells. Activation of ERK and p38 pathways might be the mechanism of higher cytotoxic effect of ATO-Indo combination.

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The Effect of Indomethacin on Paclitaxel Sensitivity and Apoptosis in Oral Squamous Carcinoma Cells<subtitle>The Role of Nuclear Factor–κB Inhibition</subtitle>

Cited by 12 publications

References 39 publications

Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel

Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel

Quantitative Proteomic Analysis of Oral Brush Biopsies Identifies Secretory Leukocyte Protease Inhibitor as a Promising, Mechanism-Based Oral Cancer Biomarker

Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

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