Prevention of chemotherapy-induced alopecia by the anti-death FNK protein.
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.
Nakashima-Kamimura
Naomi
N
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki-City, Kanagawa, Japan.
Nishimaki
Kiyomi
K
Mori
Takashi
T
Asoh
Sadamitsu
S
Ohta
Shigeo
S
D000505:Alopecia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000633:toxicity*; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D020011:Protective Agents; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D020011:Protective Agents; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D005047:Etoposide; C486257:Plk3 protein, rat; D017346:Protein Serine-Threonine Kinases