<p>Cervical cancer (CC) remains a leading malignancy among women worldwide. Current management strategies, including surgery, radiotherapy, chemotherapy, targeted therapy, and prevention, often cause significant adverse effects and demonstrate limited efficacy in advanced disease. Consequently, identifying novel therapeutic strategies and drug targets, particularly low-toxicity, high-specificity natural agents-constitutes a critical research priority. Bovine lactoferrin (bLF), a multifunctional iron-binding glycoprotein, demonstrates therapeutic potential, though its precise molecular mechanisms in cervical cancer are incompletely understood. This study therefore examined the biochemical and transcriptomic alterations in bLF-treated cervical cancer cells to elucidate its mode of action. bLF suppressed HeLa cell viability in a dose-dependent manner and concurrently promoted apoptosis while inhibiting proliferation and migration. The bLF-induced apoptosis appears to arise from a synergistic multi-mechanistic interplay, potentially involving increased intracellular ROS levels, downregulated mitochondrial membrane potential, or modulated expression of autophagy-related proteins to activate autophagic pathways. RNA sequencing identified substantial transcriptomic changes in cancer-associated pathways, notably affecting cell cycle progression, protein transport, apoptotic processes, and the negative regulation of apoptosis. These results substantiate the potent anticancer activity of bLF and highlight its promise as a therapeutic candidate derived from a natural product.</p>

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Bovine lactoferrin induces apoptosis and modulates the transcriptomic landscape of HeLa cervical cancer cells

  • Yu Zhao,
  • Rui Liu,
  • Mengtian Li,
  • Mingzhuang Feng,
  • Yuting Bao,
  • Guoxin Chen,
  • Haixia Zhang

摘要

Cervical cancer (CC) remains a leading malignancy among women worldwide. Current management strategies, including surgery, radiotherapy, chemotherapy, targeted therapy, and prevention, often cause significant adverse effects and demonstrate limited efficacy in advanced disease. Consequently, identifying novel therapeutic strategies and drug targets, particularly low-toxicity, high-specificity natural agents-constitutes a critical research priority. Bovine lactoferrin (bLF), a multifunctional iron-binding glycoprotein, demonstrates therapeutic potential, though its precise molecular mechanisms in cervical cancer are incompletely understood. This study therefore examined the biochemical and transcriptomic alterations in bLF-treated cervical cancer cells to elucidate its mode of action. bLF suppressed HeLa cell viability in a dose-dependent manner and concurrently promoted apoptosis while inhibiting proliferation and migration. The bLF-induced apoptosis appears to arise from a synergistic multi-mechanistic interplay, potentially involving increased intracellular ROS levels, downregulated mitochondrial membrane potential, or modulated expression of autophagy-related proteins to activate autophagic pathways. RNA sequencing identified substantial transcriptomic changes in cancer-associated pathways, notably affecting cell cycle progression, protein transport, apoptotic processes, and the negative regulation of apoptosis. These results substantiate the potent anticancer activity of bLF and highlight its promise as a therapeutic candidate derived from a natural product.