title: Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling.
abstract: 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.
authors.affiliation: Department of Head and Neck Surgery, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: A R
authors.initials: AR
authors.lastname: Fetoni
authors.affiliation: Department of Head and Neck Surgery, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Paciello
authors.affiliation: Institute of Human Physiology, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Mezzogori
authors.affiliation: Department of Head and Neck Surgery, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rolesi
authors.affiliation: Institute of Human Physiology, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: S L M
authors.initials: SL
authors.lastname: Eramo
authors.affiliation: Department of Head and Neck Surgery, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Paludetti
authors.affiliation: Institute of Human Physiology, Università Cattolica, School of Medicine, Largo F Vito 1, Rome 00168, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Troiani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; D050796:STAT3 Transcription Factor; D003474:Curcumin; D002945:Cisplatin