5-Fluorouracil induces apoptotic cell death with G2 phase arrest in human breast cancer grafted in nude mice.
Treatment with 5-fluorouracil and its derivatives causes DNA double strand breaks in the S phase, and the subsequent cell death. A 5-Fluorouracil derivative (UFT), that is converted to 5-fluorouracil in vivo, was administered orally at a dose of 18 mg/kg/day to nude mice bearing human breast cancer for 28 consecutive days. The tumors on day 7, 14, 21, and 28 after treatment were examined histopathologically and by flow cytometric cell cycle analysis. UFT treatment achieved remarkable inhibition of tumor growth, and histological examination revealed significantly less mitotic figures and more apoptotic bodies throughout the treated tumors, compared to the controls. Flow cytometric study showed changes in the cell cycle outflow of treated tumor cells, involving reduced numbers of G1 phase cells and increased numbers of S and G2 phase cells, compared to the corresponding controls. The reduced growth of tumors induced by UFT is attributable to a rise in apoptotic cell death as well as a decline in producing daughter cells, i.e. mitotic activity, and 5-fluorouracil may act cytotoxically on cancer cells via apoptosis, followed by arrest at G2 phase.
Department of Pathology, Osaka Teishin Hospital, Japan.
S
S
Okamoto
M
M
Sakai
J
J
Uchida
H
H
Saito
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D001835:Body Weight; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D016923:Cell Death; D004273:DNA, Neoplasm / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014183:Transplantation, Heterologous
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D005472:Fluorouracil