• Open Access

Hydroxycamptothecin-loaded Fe3O4 nanoparticles induce human lung cancer cell apoptosis through caspase-8 pathway activation and disrupt tight junctions

Authors

  • Gen Zhang,

    1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
    2. State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China
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  • Lei Ding,

    1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
    2. Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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  • Randall Renegar,

    1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
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  • Xuemei Wang,

    Corresponding author
    1. State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China
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  • Qun Lu,

    1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
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  • Shouquan Huo,

    1. Department of Chemistry, East Carolina University, Greenville, North Carolina, USA
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  • Yan-Hua Chen

    Corresponding author
    1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
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To whom correspondence should be addressed.
E-mail: cheny@ecu.edu; xuewang@seu.edu.cn

Abstract

10-Hydroxycamptothecin (HCPT) elicits strong anti-cancer effects and is less toxic than camptothecin (CPT), making it widely used in recent clinical trials. However, its low solubility limits its application as an effective anti-cancer therapy. In the present study we investigate the hypothesis that the unique water dispersible oleic acid-Triton X-100-coated Fe3O4 nanoparticles loaded with HCPT disrupt epithelial cell–cell junctions and induce human lung cancer cell apoptosis through the caspase-8 pathway. We characterized the HCPT-loaded nanoparticles and determined their effects on lung cancer cell viability and apoptosis by using immunofluorescence light microscopy and SDS-PAGE/immunoblots. We found that HCPT-loaded nanoparticles elicited an anti-proliferative effect in a dose-dependent manner. HCPT-loaded nanoparticles reduced the expression of cell–cell junction protein claudins, E-cadherin and ZO-1, and transmission electron microcopy demonstrated a disrupted tight junction ultrastructure. Transepithelial electric resistance was also reduced, indicating the reduction of tight junction functions. The HCPT-loaded nanoparticles increased phosphorylation of p38 and SAPK/JNK while it showed no effects on p42/44 MAP kinase. Compared with void Fe3O4 nanoparticles or HCPT drug alone, HCPT drug-loaded nanoparticles evoked synergistic effects by increasing cell apoptosis with enhanced activation of the caspase-8 pathway. Therefore, our current study highlights the potential of HCPT drug-loaded nanoparticles as a chemotherapeutic agent for increasing anti-cancer drug efficacy. (Cancer Sci 2011; 102: 1216–1222)

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