title: The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo.
abstract: Supranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Hui
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Duan
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: An
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Pa
authors.initials: P
authors.lastname: Wu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Ci
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, NO. 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: cmxu@ibms.pumc.edu.cn.
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D020887:Selenious Acid / Q000737:chemistry*; D050396:TRPP Cation Channels / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D020887:Selenious Acid; D050396:TRPP Cation Channels; D048051:p38 Mitogen-Activated Protein Kinases; C115163:CREB1 protein, human
keywords: Apoptosis; CREB; PKD1; Selenite; p38 MAPK