title: Atmospheric particulate matter (PM10) exposure-induced cell cycle arrest and apoptosis evasion through STAT3 activation via PKCζ and Src kinases in lung cells.
abstract: Atmospheric particulate matter with aerodynamic diameter ≤10 μm (PM10) is a risk factor for the development of lung cancer, but cellular pathways are not completely understood. STAT3 is a p21(Waf1/Cip1) transcription factor and is associated with proliferation and cell survival and is upregulated in lung cancer. PM10 exposure induces p21(Waf1/Cip1) expression, which could be related to STAT3 activation. The aims of this work were to investigate whether STAT3 was activated on lung epithelial cells after PM10 exposure and to determine whether or not STAT3 could have an impact on cell cycle distribution and cell survival. Our results showed that PM10 induced STAT3 activation through Src and PKCζ kinases, and it is partially responsible for the p21(Waf1/Cip1) induction that was also observed. Moreover, PM10 induced G1-G0 cell cycle arrest. The inhibition of STAT3 phosphorylation prevented cell cycle arrest and triggered apoptosis. These results suggest that PM10 exposure might activate a survival pathway related to STAT3 activation, similar to what has been described as part of the immune system and apoptosis evasion during tumor promotion and development.
authors.affiliation: Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico; Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, 09340, México DF, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Reyes-Zárate
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080, México DF, Mexico.
authors.forename: Yesennia
authors.initials: Y
authors.lastname: Sánchez-Pérez
authors.affiliation: Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, 09340, México DF, Mexico.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Gutiérrez-Ruiz
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, 54059, Estado de México, Mexico.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada.
authors.forename: Álvaro Román
authors.initials: ÁR
authors.lastname: Osornio-Vargas
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080, México DF, Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: Morales-Bárcenas
authors.affiliation: Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, 09340, México DF, Mexico. Electronic address: veso@xanum.uam.mx.
authors.forename: Verónica
authors.initials: V
authors.lastname: Souza-Arroyo
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080, México DF, Mexico. Electronic address: claudia.garciac@salud.gob.mx.
authors.forename: Claudia María
authors.initials: CM
authors.lastname: García-Cuellar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D052638:Particulate Matter; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019061:src-Family Kinases; D011493:Protein Kinase C
keywords: Atmospheric particulate matter (PM(10)); PKCζ kinase; STAT3; Src kinase; p21(Waf1/Cip1)