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Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway.
Lv, Cunqi; Zeng, Qingyu; Qi, Lei; Wang, Yuanyuan; Li, Jiacheng; Sun, Huixin; Du, Linlin; Hao, Shuxiu; Li, Guijin; Feng, Chen; Zhang, Yu; Wang, Cheng; Wang, Xinshu; Ma, Rong; Wang, Tong; Li, Qi.
Afiliación
  • Lv C; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Zeng Q; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Qi L; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Wang Y; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Li J; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Sun H; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Du L; School of Public Health, Qiqihar Medical University, Qiqihar 161003, China.
  • Hao S; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Li G; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Feng C; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Zhang Y; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Wang C; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Wang X; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Ma R; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
  • Wang T; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health, Harbin Medical University, Harbin 150081, China.
  • Li Q; Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.
Antioxidants (Basel) ; 13(8)2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39199249
ABSTRACT
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Antioxidants (Basel) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Antioxidants (Basel) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza