Prevention of chemotherapy-induced alopecia by the anti-death FNK protein

Life Sci. 2008 Jan 16;82(3-4):218-25. doi: 10.1016/j.lfs.2007.11.011. Epub 2007 Dec 3.

Abstract

Many anticancer drugs attack rapidly dividing cells, including not only malignant cells but also hair follicle cells, and induce alopecia. Chemotherapy-induced alopecia (CIA) is an emotionally distressing side effect of cancer chemotherapy. There is currently no useful preventive therapy for CIA. We have previously constructed anti-death rFNK protein from rat Bcl-x(L) by site-directed mutagenesis to strengthen cytoprotective activity. When fused to the protein transduction domain (PTD) of HIV/Tat, the fusion protein PTD (TAT)-rFNK successfully entered cells from the outside in vitro and in vivo to exhibit anti-death activity against apoptosis and necrosis. Here, we show that topical application of FNK protected against CIA in a newborn rat model. The protective activity against hair-loss was observed in 30-1000 nM TAT-rFNK administrative groups in a dose-dependent manner. Furthermore, a human version of FNK (hFNK) fused to other PTD peptides exhibited a protective ability. These results suggest that PTD-FNK possesses protective activity against CIA and is not restricted to a sequence of PTD peptides or species of FNK. Thus, PTD-FNK represents potential to develop a useful method for preventing CIA in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / chemically induced
  • Alopecia / pathology
  • Alopecia / prevention & control*
  • Animals
  • Animals, Newborn
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Etoposide / toxicity*
  • Hair Follicle / drug effects
  • Hair Follicle / metabolism
  • Hair Follicle / pathology
  • Humans
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Protective Agents
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / therapeutic use*
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / therapeutic use*
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cell Cycle Proteins
  • Protective Agents
  • Recombinant Fusion Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Etoposide
  • Plk3 protein, rat
  • Protein Serine-Threonine Kinases