Inorganics (Nov 2021)

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug

  • Louis J. Delinois,
  • Omar De León-Vélez,
  • Adriana Vázquez-Medina,
  • Alondra Vélez-Cabrera,
  • Amanda Marrero-Sánchez,
  • Christopher Nieves-Escobar,
  • Daniela Alfonso-Cano,
  • Delvin Caraballo-Rodríguez,
  • Jael Rodriguez-Ortiz,
  • Jemily Acosta-Mercado,
  • Josué A. Benjamín-Rivera,
  • Kiara González-González,
  • Kysha Fernández-Adorno,
  • Lisby Santiago-Pagán,
  • Rafael Delgado-Vergara,
  • Xaiomy Torres-Ávila,
  • Andrea Maser-Figueroa,
  • Gladimarys Grajales-Avilés,
  • Glorimar I. Miranda Méndez,
  • Javier Santiago-Pagán,
  • Miguel Nieves-Santiago,
  • Vanessa Álvarez-Carrillo,
  • Kai Griebenow,
  • Arthur D. Tinoco

DOI
https://doi.org/10.3390/inorganics9110083
Journal volume & issue
Vol. 9, no. 11
p. 83

Abstract

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The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.

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