Experimental Studies of the Protective Effect of Deferoxamine Mesilate on Cisplatin-induced Toxicity.

Watanabe, Hironobu; Kanno, Hidetaka

doi:10.3950/jibiinkoka.101.8_967

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…Inhibition of EGFR activation has been shown to suppress the growth of human cancer cells [37], [38]. Moreover, most of the cancers acquire drug resistance due to the activation of EGFR pathway [3], [39]. Therefore, inhibiting EGFR could be one potential approach to treat ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

et al. 2012

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Ovarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 µmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

et al. 2012

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“…The results of some studies suggest that CDDP-induced ATN is prevented by iron chelators or other types of antioxidant agents as well. All of these benefits stem from the fact that CDDP toxicity results from free radical damage and these agents function to reduce free radicals [4]. Hannemann et al [28] found that antioxidants lowered CDDP-induced MDA production.…”

Section: Discussionmentioning

confidence: 99%

Physiological and pharmacological concentrations of melatonin protect against cisplatin‐induced acute renal injury

Parlakpınar

Şahna

Özer

et al. 2002

Journal of Pineal Research

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Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side-effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham-operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP-induced renal injury.

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“…Iron chelators render cochlear iron stores less reactive with hydrogen peroxide, thereby inhibiting the Fenton reaction. Iron chelators such as deferoxamine (DFO) and dihydroxybenzoate (DHB) have successfully attenuated hearing loss due to acoustic trauma, 49 cisplatin, 71 and aminoglycosides when given before the insult. Addition of GSH to animals on a restricted protein diet resulted in reduced ototoxicity from gentamicin.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

A Radical Demise: Toxins and Trauma Share Common Pathways in Hair Cell Death

Kopke

Allen

Henderson³

et al. 1999

Annals of the New York Academy of Sciences

164

132

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The pathologic similarities noted after ototoxic and/or traumatic injury to the cochlea as well as the key features of the cochlea that make it susceptible to reactive oxygen species (ROS) damage are reviewed. Recent evidence linking ROS to cochlear damage associated with both ototoxins and/or trauma are presented. Mechanisms of generation of ROS in the cochlea and how these metabolites damage the cochlea and impair function are also reviewed. Finally, examples of novel therapeutic strategies to prevent and reverse hearing loss due to noise and/or ototoxins are presented to illustrate the clinical relevance of these new findings.

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Experimental Studies of the Protective Effect of Deferoxamine Mesilate on Cisplatin-induced Toxicity.

Cited by 16 publications

References 37 publications

Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

Physiological and pharmacological concentrations of melatonin protect against cisplatin‐induced acute renal injury

A Radical Demise: Toxins and Trauma Share Common Pathways in Hair Cell Death

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