Repositioning of anti-viral drugs as therapy for cervical cancer

Sapna Sharma1, Ruma Baksi2, Milee Agarwal3

  • 1Department of Pharmacology and Toxicology, NIPER-Ahmedabad, C/o B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Thaltej-Gandhinagar Highway, Ahmedabad 380054, Gujarat, India.

Abstract

Insights

Ribavirin and Indinavir show promise in fighting HPV-18 cervical cancer by inhibiting eIF4E. These drugs reduced cancer cell viability and tumor growth in preclinical studies.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Human Papilloma Virus (HPV) oncogenic proteins increase Eukaryotic translation initiation factor 4E (eIF4E) expression, contributing to HPV-induced carcinogenesis.
  • eIF4E plays a critical role in the development of HPV-related cancers.
  • Ribavirin and Indinavir are known inhibitors of eIF4E activity.

Purpose of the Study:

  • To investigate the therapeutic potential of Ribavirin and Indinavir against HPV-18 induced cervical cancer.
  • To assess the effects of Ribavirin and Indinavir on cancer cell viability, apoptosis, and matrix metalloproteinase (MMP) secretion.
  • To evaluate the in vivo efficacy of Ribavirin in reducing tumor volume.

Main Methods:

  • In vitro assays on HeLa cells: MTT and Neutral red assays for cell viability, Caspase activity assays for apoptosis, and Gelatinase activity assays for MMP-2 and MMP-9 secretion.
  • In vivo study using human xenografts in immunocompromised C57BL/6 mice to assess Ribavirin's effect on tumor volume.

Main Results:

  • Ribavirin and Indinavir demonstrated significant reduction in HeLa cell viability in vitro.
  • Both drugs induced apoptosis and decreased MMP secretion in vitro.
  • Daily treatment with Ribavirin (50mg/kg and 100mg/kg) resulted in a significant decrease in tumor volume in vivo.

Conclusions:

  • Ribavirin and Indinavir exhibit anti-cancer properties against HPV-18.
  • These drugs can be considered as potential therapeutic agents for HPV-18 induced cervical cancer.

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