2. Academic Validation
  3. Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming

Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming

  • Life Sci. 2024 Nov 15:357:123109. doi: 10.1016/j.lfs.2024.123109.
Qingyu Zeng 1,  Cunqi Lv 2,  Lei Qi 3,  Yuanyuan Wang 2,  Shuxiu Hao 2,  Guijin Li 2,  Huixin Sun 2,  Linlin Du 2,  Jiacheng Li 2,  Cheng Wang 2,  Yu Zhang 2,  Xinshu Wang 4,  Rong Ma 5,  Tong Wang 6,  Qi Li 7
Affiliations

Affiliations

  • 1 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China. Electronic address: 2022020090@hrbmu.edu.cn.
  • 2 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
  • 3 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; School of Public Health, Qiqihar Medical University, Qiqihar 161003, Heilongjiang, China.
  • 4 Nanchang University Queen Mary School, Nanchang 330000, China.
  • 5 Department of Gynecological Oncoology, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address: marong@hrbmu.edu.cn.
  • 6 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China. Electronic address: wangtong@ems.hrbmu.edu.cn.
  • 7 Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address: liqi@ems.hrbmu.edu.cn.
PMID: 39384146 DOI: 10.1016/j.lfs.2024.123109
Abstract

Aims: This study aims to explore the inhibitory effect of selenium on cervical Cancer through suppression of glucose metabolic reprogramming and its underlying mechanisms.

Methods: Sodium selenite (SS) treated HeLa and SiHa cells were assessed for proliferation using the CCK-8 assay and immunofluorescence. DNA synthesis was measured with the EdU assay. A nude mouse xenograft model evaluated SS's anti-cervical Cancer effects. Reactive Oxygen Species (ROS) and mitochondrial membrane potential were measured using flow cytometry, DCFH-DA, and JC-1 probes, respectively. Apoptosis was detected via Annexin V/PI staining and Western blot. Glucose uptake, lactate production, and ATP generation were determined using 2-NBDG probes and assay kits. The mRNA and protein levels of glycolysis-related genes HK2, GLUT1, and PDK1 were measured using RT-qPCR and Western blot.

Key findings: SS inhibited HeLa and SiHa cells viability in a dose- and time-dependent manner. Intraperitoneal injection of SS in nude mice significantly inhibited HeLa cell xenograft growth without evident hepatotoxicity or nephrotoxicity. SS inhibited glucose metabolic reprogramming in Cancer cells primarily via ROS-mediated Akt/mTOR/HIF-1α pathway inhibition. Pretreatment with N-acetylcysteine (NAC) or MHY1485 (an mTOR Activator) partially reversed the inhibitory effects of SS on glucose metabolic reprogramming, cell proliferation, and migration, as well as its pro-apoptotic effects.

Significance: SS exhibited anti-cervical Cancer effects, likely through the induction of ROS generation and inhibition of glucose metabolic reprogramming in cervical Cancer cells, thereby inhibiting cell proliferation and promoting Apoptosis. These findings provide new insights into understanding the molecular mechanisms underlying SS for potential new drug development for cervical Cancer.

Keywords

AKT/mTOR/HIF-1α pathway; Cervical cancer; Glucose metabolic reprogramming; RNA sequencing; ROS; Sodium selenite.

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