Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models

Casares, Celia; Ramírez‐Camacho, Rafael; Trinidad, Almudena; Roldán, Amaya; Jorge, Eduardo; García-Berrocal, José Ramón

doi:10.1007/s00405-012-2029-0

Cited by 140 publications

(120 citation statements)

References 31 publications

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“…To verify the resistance of A549 cells to anti-cancer drug, we first compared the cytotoxicity of cisplatin in A549 and HEK293 cells. Cisplatin, one of the most potent and widely used anti-cancer drugs, leads to cell death via increased generation of ROS (Casares et al, 2012). As shown in Fig.…”

Section: A549 Cells Are Less Susceptible To Cisplatin Cytotoxicity Anmentioning

confidence: 99%

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

Lim

Lee

Cho

et al. 2013

Molecules and Cells

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator for the protection of cells against oxidative and xenobiotic stresses. Recent studies have demonstrated that high constitutive expression of Nrf2 is observed in many types of cancer cells showing resistance to anti-cancer drugs, suggesting that the suppression of overexpressed Nrf2 could be an attractive therapeutic strategy to overcome cancer drug resistance. In the present study, we aimed to find small molecule compounds that enhance the sensitivity of tumor cells to cisplatin induced cytotoxicity by suppressing Nrf2-mediated defense mechanism. A549 lung cancer cells were shown to be more resistant to the anti-cancer drug cisplatin than HEK293 cells, with higher Nrf2 signaling activity; constitutively high amounts of Nrf2-downstream target proteins were observed in A549 cells. Among the three chalcone derivatives 4-methoxy-chalcone (4-MC), hesperidin methylchalcone, and neohesperidin dihydrochalcone, 4-MC was found to suppress transcriptional activity of Nrf2 in A549 cells but to activate it in HEK293 cells. 4-MC was also shown to down-regulate expression of Nrf2 and the downstream phase II detoxifying enzyme NQO1 in A549 cells. The PI3K/Akt pathway was found to be involved in the 4-MC-induced inhibition of Nrf2/ARE activity in A549 cells. This inhibition of Nrf2 signaling results in the accelerated generation of reactive oxygen species and exacerbation of cytotoxicity in cisplatin-treated A549 cells. Taken together, these results suggest that the small molecule compound 4-MC could be used to enhance the sensitivity of tumor cells to the therapeutic effect of cisplatin through the regulation of Nrf2/ARE signaling.

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Section: A549 Cells Are Less Susceptible To Cisplatin Cytotoxicity Anmentioning

confidence: 99%

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

Lim

Lee

Cho

et al. 2013

Molecules and Cells

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“…One of the dose-limiting side effects of cisplatin is ototoxicity, which manifests as tinnitus and/or bilateral sensorineural hearing loss in the clinical setting. [1][2][3][4] Ototoxicity caused by cisplatin has effects on a number of inner ear structures, including the stria vascularis, supporting cells, spiral ganglion cells, and outer hair cells (OHCs). 2,5,6 However, the OHCs appear to be the most susceptible to damage.…”

mentioning

confidence: 99%

Cisplatin‐Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a Mouse Model

Naples

Parham

2015

Otolaryngol.--head neck surg.

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Objective. To evaluate whether the calcium-channel blocker diltiazem has protective effects against cisplatin-induced ototoxicity in a mouse model. Study Design. Original basic science in vivo investigation.Setting. Academic setting: Otolaryngology-Head and Neck Surgery laboratory at University of Connecticut Health Center.Subjects. Thirty-nine female CBA/J mice.Methods. Pure tone-or click-evoked auditory brainstem responses (ABRs) were recorded in CBA/J mice to determine auditory thresholds. All mice had baseline ABRs recorded. They were then given a single cisplatin bolus (14 mg/kg), followed by 5 consecutive days of intratympanic diltiazem or saline control. Follow-up thresholds were recorded on days 7, 14, and 21 postcisplatin. Tone-evoked ABRs evaluated the otoprotective effect of 2-mg/kg diltiazem in 9 mice, and dose effect was examined in response to click-evoked ABR with 2-or 4-mg/kg diltiazem in 2 groups of 15 mice.Results. Saline-treated ears had significantly elevated toneevoked auditory thresholds when compared with diltiazemtreated ears (P = .038) on day 7 postcisplatin only. Clickevoked ABR thresholds were significantly elevated in salinetreated ears versus diltiazem-treated ears for the 2-mg/kg group (P = .001) and 4-mg/kg group (P = .011) on days 7, 14, and 21 postcisplatin. Conclusion.Intratympanic diltiazem has significant protective effects against cisplatin ototoxicity at 2 and 4 mg/kg. This is the first in vivo study to demonstrate that diltiazem offers a potentially novel therapy for cisplatininduced ototoxicity.

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“…Recent biochemical analysis documents a number of protein variants for VLGR1, cadherin 23, and protocadherin 15 in the cochlea and the retina (Lagziel et al, 2009;Zallocchi et al, 2012). Due to the involvement of ROS generation and inflammation mediators in cisplatin toxicity (Casares et al, 2012), and these common characteristics, there is a strong rationale for testing lutein as a protective agent against cisplatin-induced damage due to its antioxidant and anti-inflammatory activity. Previous in vivo studies on lutein employ systemic administra-tion routes.…”

Section: Discussionmentioning

confidence: 99%

“…Many experimental studies have attempted to evaluate different substances against ROS overload and other cell signaling systems at an early stage to stop the apoptotic pathways. There is a clear rationale behind the testing of antioxidants against cisplatin ototoxicity as the overload of ROS after cisplatin administration has been shown to be one of the main mechanisms triggering death pathways inside auditory sensory cells (Casares et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

Fidalgo

Saldaña²,

Trinidad

et al. 2016

Experimental and Toxicologic Pathology

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Experimental and Toxicologic Pathology 68.4 (2016): 197-204 A B S T R A C TIntroduction: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases.Aim: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity.Materials and Methods: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 mM) and to 25 mM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min,1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy.Results: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 mM. In vivo study: Intratympaniclutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats.Conclusions: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result

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Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models

Cited by 140 publications

References 31 publications

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

Cisplatin‐Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a Mouse Model

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

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