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The molecular response of vanadium complexes of nicotinoyl hydrazone in cervical cancers--a possible interference

Rakesh S Nair1, Mini Kuriakose2, Veena Somasundaram1

  • 1Cancer Research Program 5, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014 Kerala, India.

Life Sciences
|September 27, 2014
PubMed
Abstract

Insights

Novel vanadium complexes show promise in treating Human Papillomavirus (HPV)-infected cervical cancers. OVK 49 effectively induces apoptosis and downregulates oncogenes in HPV16-positive cells, suggesting a new therapeutic avenue.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Virology

Background:

  • Hydrazones, specifically NNO donor Schiff bases, possess known anti-viral and anti-neoplastic properties.
  • Certain cancers, including colon, hepatocellular, and testicular cancers, have shown susceptibility to hydrazone-based therapies.
  • Human Papillomavirus (HPV) infection is a significant risk factor for cervical cancer development.

Purpose of the Study:

  • To investigate the anti-cancer effects of two novel nicotinoyl hydrazones on Human Papillomavirus (HPV) infected cervical cancer cells.
  • To evaluate the potential of these compounds in targeting HPV-driven malignancies.
  • To explore the underlying molecular mechanisms of action.

Main Methods:

  • Utilized MTT assay to assess the impact of vanadium complexes on SiHa (HPV16-positive) and HeLa (HPV18-positive) cell proliferation.
  • Determined apoptotic potential by measuring DNA condensation and mitochondrial membrane potential loss.
  • Analyzed caspase activity and DNA content to understand apoptosis induction pathways.
  • Employed RT-PCR to examine the expression of cell cycle regulatory genes (GADD45, p53, p21) and HPV oncogenes (E6, E7).

Main Results:

  • OVK 49 demonstrated superior apoptosis-inducing capabilities compared to OVK 89 in HPV16-positive SiHa cells.
  • Treatment with OVK 49 led to downregulation of E6 and E7 mRNA transcripts in SiHa cells.
  • OVK 49 treatment resulted in the induction of p53 protein expression in SiHa cells.
  • These findings suggest OVK 49 possesses significant anti-cancer activity against HPV16-positive cervical cancers.

Conclusions:

  • This study provides the first evidence that specific vanadium complexes can trigger a p53-dependent apoptotic pathway.
  • The observed mechanism is particularly relevant for high-risk HPV16-positive cervical cancers.
  • Vanadium complexes represent a promising therapeutic strategy for HPV-associated cervical malignancies.
Keywords:
HPV16-positiveNicotinoyl hydrazonesOxidovanadiumSiHa

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