Naproxen-induced Ca<sup>2+</sup> movement and death in MDCK canine renal tubular cells

Hh, Cheng; Ct, Chou; Tk, Sun; Wz, Liang; Js, Cheng; Ht, Chang; Hw, Tseng; Cc, Kuo; Chen, Fa; Dh, Kuo; Shieh, Pochuen; Cr, Jan

doi:10.1177/0960327115569810

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…Other important mechanisms of parthenolide action include DNA synthesis inhibition (58), mitochondrial disorder induction, G 2 /M cell cycle arrest (44,53) and sustained activation of c-Jun N-terminal kinase (JNK) (42). In addition, alternation in Ca 2+ homeostasis is also involved in the bioactivity of parthenolide (47) to induce apoptosis through multiple pathways (12,13,22,37,50). Likewise, it has also been reported that parthenolide induced downregulation of a variety of antiapoptotic molecules, such as Bcl-xL, Mcl-1 and survivin in leukemia cells (31).…”

Section: Introductionmentioning

confidence: 99%

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

et al. 2015

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Chemotherapy efficacy is limited by intrinsic and acquired resistance in glioblastoma (GBM); hence, novel tactics are crucial. Survivin has been demonstrated as a key resistant factor in GBM because of its function in inhibiting apoptosis, regulating autophagy, and in promoting G₂/M cell cycle transition. Parthenolide has been reported to be an effective antitumor agent in a variety of tumor cells and decreases survivin level in leukemia cells. But the effect of parthenolide on survivin and the cell death process in GBM is still unknown. The aim of this study was to examine whether parthenolide had the potential to inhibit cell proliferation in the GBM cell line U373. The parthenolide-induced effects in relation to survivin suppression and cell death were further investigated. Our results showed that parthenolide substantially inhibited cell viability with IC₅₀ values of approximate 16 μM. Treatment with parthenolide at the dose of 16 μM led to considerable downregulation of survivin, G₂/M cell cycle arrest and Chk2 upregulation in cells. Parthenolide induced apoptosis in only a few cells and a slight increase in activated caspases 3 levels. By contrast, parthenolide induced a significant increase of intracellular autophagosomes and the expression of autophagy related proteins, including ULK1 and LC3 I/LC3 II, in the treated cells. These results suggested that parthenolide induced survivin inhibition, G₂/M cell cycle arrest, and triggered cell death through autophagic cell death in the GBM cell line.

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Section: Introductionmentioning

confidence: 99%

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

et al. 2015

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“…The affinity of hOCT2 for ASP + was determined by saturation experiments of specific ASP + uptake determined in the presence of increasing ASP + concentrations (0–50 µM). In further experiments, regulation of hOCT2-mediated transport was evaluated by the co-incubation of ASP + with 1 nM AII, or 1 µM DOG (a PKC activator, this concentration is known to be able to regulate OCT-activity [ 65 ]), or 40 µM rottlerin (a PKC inhibitor), or 5 µM BAPTA-AM (a Ca 2+ chelator, this concentration efficiently chelates intracellular Ca 2+ and does not compromise cell viability in MDCK cells [ 66 ]), alone or in combination. Solvents (DMSO or ethanol) at the concentration used in the regulation experiments did not change the ASP + uptake (not shown).…”

Section: Methodsmentioning

confidence: 99%

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Kantauskaitè

Hucke

Snieder

et al. 2022

IJMS

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Cisplatin (CDDP) is an efficient chemotherapeutic drug, whose use is associated with the development of serious undesired toxicities, such as nephrotoxicity. The human organic cation transporter 2 (hOCT2), which is highly expressed in the basolateral membrane domain of renal proximal tubules seems to play an important role in the development of CDDP nephrotoxicity. The role of angiotensin II (AII) signaling by binding to the AII receptor type 1 (AT1R) in the development and/or progression of CDDP nephrotoxicity is debated. Therefore, in this work, the regulation of hOCT2 activity by AII and its role in the development of CDDP cellular toxicity was investigated. To do this, hOCT2 was overexpressed by viral transduction in Madin–Darby Canine Kidney (MDCK) cells which were cultivated on a filter. This approach allows the separation of an apical and a basolateral membrane domain, which are easily accessible for experimentation. In this system, hOCT2 was mainly localized on the basolateral plasma membrane domain of the cells. The transporter was functional since a specific uptake of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) with an affinity (Km) of 35 µM was only detectable by the addition of ASP+ to the basolateral compartment of hOCT2 expressing MDCK (hOCT2-MDCK) cells. Similarly, CDDP toxicity was evident mainly by CDDP addition to the basolateral compartment of hOCT2-MDCK cells cultivated on a filter. The addition of 1 nM AII stimulated hOCT2 function via PKC activation and worsened CDDP cytotoxicity via binding to AT1R. Therefore, the AII signaling pathway may be implicated in the development and/or progression of CDDP nephrotoxicity. This signaling pathway may be a target for protective interventions for example by blocking AT1R in the kidneys. However, it should be further investigated whether these findings obtained in a cell culture system may have translational relevance for the clinical situation. For toxicity experiments, a 100 µM CDDP concentration was used, which is high but allows us to identify clearly toxic effects due to hOCT2. In summary, down-regulation of hOCT2 activity by the inhibition of the AII signaling pathway may protect against CDDP nephrotoxicity.

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“…NSAIDs eliminate pain, but do not eliminate signs and symptoms of active disease, nor do they repair cartilage. Furthermore, the use of NSAIDs can be linked to side effects, such as hepatic and renal dysfunction [47][48][49] reduced appetite, vomiting, and gastrointestinal upset and bleeding [50][51][52][53][54]. Additionally, NSAIDs have been reported to inhibit bone healing [55].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

Murdock¹,

Vega³

et al. 2015

J Veterinar Sci Technol

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The present investigation was undertaken to assess anti-inflammatory and anti-arthritic efficacy and safety of T. chebula extract (TCE) in moderately osteoarthritic (OA) dogs. Dogs with OA received either 500 mg placebo or 500 mg TCE twice daily for 150 days. On a monthly basis, dogs were given a full physical exam and were evaluated for arthritic pain (overall pain, pain upon limb manipulation, and pain after physical exertion), inflammation (erythrocyte sedimentation rate, ESR), and analysis of complete blood count (CBC) and serum biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine), and heart and skeletal muscle (CK) functions. Elbow and stifle joints were radiographed on day 0 and day 150 for evaluation of arthritic progression. Dogs given TCE showed significant (P<0.01) reductions in overall pain, pain upon limb manipulation, and pain after physical exertion by day 90, with maximum effects on day 150 (81.2%, 81.5%, and 84.2%, respectively). A marked reduction in ESR coincided with pain reduction in TCE-treated dogs, which was indicative of anti-inflammatory effect of TCE. Radiographic evidence also indicated slowed progression of OA in joints examined. No significant change occurred in physical parameters, CBC parameters, or serum biomarkers in dogs on placebo or treatment, which suggested that TCE was well tolerated. It can be concluded that TCE, by having many active principles (chebulagic acid, chebulinic acid, corilagin, hydrolysable tannoids, etc.) might have provided antioxidant, anti-inflammatory and anti-arthritic effects in dogs without causing any side effects.

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Naproxen-induced Ca²⁺ movement and death in MDCK canine renal tubular cells

Cited by 3 publications

References 31 publications

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

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Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells

Cited by 3 publications

References 31 publications

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

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Naproxen-induced Ca²⁺ movement and death in MDCK canine renal tubular cells