title: Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells.
abstract: Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.
authors.affiliation: Departamento de Morfologia y Biologia Celular, Biology Unit, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Rodriguez-Garcia
authors.affiliation: Departamento de Morfologia y Biologia Celular, Biology Unit, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, Spain; Research and Development Department, Bioquochem S.L., Parque Tecnológico de Asturias, 33428 Llanera, Asturias, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hevia
authors.affiliation: Departamento de Morfologia y Biologia Celular, Biology Unit, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mayo
authors.affiliation: Departamento de Morfologia y Biologia Celular, Biology Unit, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez-Menendez
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolisnka Institute, SE-17177 Stockholm, Sweden.
authors.forename: Lucia
authors.initials: L
authors.lastname: Coppo
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolisnka Institute, SE-17177 Stockholm, Sweden.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolisnka Institute, SE-17177 Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Departamento de Morfologia y Biologia Celular, Biology Unit, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, Spain. Electronic address: sainzrosa@uniovi.es.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sainz
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D012838:Silymarin; D013267:Stilbenes; C491203:TXN protein, human; C486715:TXNIP protein, human; D000077385:Silybin; D013879:Thioredoxins; D003474:Curcumin; D008550:Melatonin; D000077185:Resveratrol
keywords: Apoptosis; Prostate cancer; Redox signaling; TXNIP; Thioredoxin; Thioredoxin reductase