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Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling
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Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling
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Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling
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Journal Article
Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling
2015
Overview
Background:
In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance
in vitro
and the adverse effect ototoxicity
in vivo
.
Methods:
The effects of curcumin and/or cisplatin treatment have been evaluated in head and neck squamous cell carcinoma as well as in a rat model of cisplatin-induced ototoxicity by using immunofluorescence, western blot, and functional and morphological analysis.
Results:
This study demonstrates that curcumin attenuates all stages of tumour progression (survival, proliferation) and, by targeting pSTAT3 and Nrf-2 signalling pathways, provides chemosensitisation to cisplatin
in vitro
and protection from its ototoxic adverse effects
in vivo.
Conclusions:
These results indicate that curcumin can be used as an efficient adjuvant to cisplatin cancer therapy. This treatment strategy in head and neck cancer could mediate cisplatin chemoresistance by modulating therapeutic targets (STAT3 and Nrf2) and, at the same time, reduce cisplatin-related ototoxic adverse effects.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antineoplastic Agents - administration & dosage
/ Antineoplastic Agents - adverse effects
/ Biomedical and Life Sciences
/ Carcinoma, Squamous Cell - drug therapy
/ Carcinoma, Squamous Cell - metabolism
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Cisplatin - administration & dosage
/ Curcumin - administration & dosage
/ Drug Resistance, Neoplasm - drug effects
/ Evoked Potentials, Auditory, Brain Stem - drug effects
/ Head and Neck Neoplasms - drug therapy
/ Head and Neck Neoplasms - metabolism
/ Hearing Loss - chemically induced
/ Hearing Loss - prevention & control
/ Humans
/ Male
/ NF-E2-Related Factor 2 - metabolism
/ Oncology
/ Phosphorylation - drug effects
/ Rats
/ Signal Transduction - drug effects
