PMID- 17504194
OWN - NLM
STAT- MEDLINE
DCOM- 20070725
LR  - 20191026
IS  - 1573-4064 (Print)
IS  - 1573-4064 (Linking)
VI  - 3
IP  - 3
DP  - 2007 May
TI  - 5-fluorouracil derivatives induce differentiation mediated by tubulin and HLA 
      class I modulation.
PG  - 233-9
AB  - Neoplastic cells exhibit defects in their ability to differentiate; therefore, 
      differentiation therapy represents a viable option to control cancer growth and 
      progression. Rhabdomyosarcomas (RMS), a malignant tumor of skeletal muscle, is 
      the most common soft tissue sarcoma in children and is characterized by its poor 
      response to cytotoxic treatment and significant morbidity. Since modulation of 
      alpha-tubulin and human leukocyte antigen (HLA) class I expression has been 
      detected during malignant transformation, we analyzed in this study the 
      expression pattern of both kinds of proteins after the treatment with 5-FU 
      derivatives in the human RMS RD cell line. Cytotoxic assays, scanning and 
      transmission electron microscopy, flow cytometry and immunocytochemical analyses 
      were used. The compounds analyzed belonged to the following three categories: (a) 
      symmetrical bis(5-fluorouracil-1-yl) derivatives with a linker that connects the 
      N(1) atoms of both pyrimidine moieties by means of two amide bonds; and (b) an 
      ester with the 5-FU base. The whole structure corresponds to the terminal 
      fragment of the molecules included in (a) and (c) 5-fluorouracil 
      acyclonucleoside-like structures. 
      1-[[3-(3-Chloro-2-hydroxypropoxy)-1-methoxy]propoxy]propyl]-5-fluorouracil (2), 
      that belongs to the class (a) produced the highest increment of tubulin and its 
      intense capillary distribution throughout the cytoplasm. On the other hand, 
      N,N-bis[3-(5-fluorouracil-1-yl)-3-methoxypropanoyl]-alpha,alpha;-diamino-m-xylene 
      (5) and 2 that are included in the class (c) caused the major percentage of 
      marked cells by the HLA class I proteins. In short, our results showed that the 
      5-FU derivatives increase HLA class I expression and showed greater microtubule 
      stability with an important network of tubulin beams related with the degree of 
      differentiation of RD cells. These results could mean a more favorable prognosis 
      of the patients affected with these tumors.
FAU - Marchal, Juan A
AU  - Marchal JA
AD  - Departamento de Ciencias de la Salud, Universidade de Jaen, Jaen, Spain.
FAU - Boulaiz, Houria
AU  - Boulaiz H
FAU - Rodriguez-Serrano, Fernando
AU  - Rodriguez-Serrano F
FAU - Peran, Macarena
AU  - Peran M
FAU - Carrillo, Esmeralda
AU  - Carrillo E
FAU - Velez, Celia
AU  - Velez C
FAU - Dominguez, Jose
AU  - Dominguez J
FAU - Gomez-Vidal, Jose A
AU  - Gomez-Vidal JA
FAU - Campos, Joaquin
AU  - Campos J
FAU - Gallo, Miguel A
AU  - Gallo MA
FAU - Espinosa, Antonio
AU  - Espinosa A
FAU - Aranega, Antonia
AU  - Aranega A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Med Chem
JT  - Medicinal chemistry (Shariqah (United Arab Emirates))
JID - 101240303
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Tubulin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antimetabolites, Antineoplastic/chemistry/pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Fluorouracil/*analogs & derivatives/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - Microtubules/drug effects
MH  - Rhabdomyosarcoma/drug therapy/pathology
MH  - Structure-Activity Relationship
MH  - Tubulin/*genetics
EDAT- 2007/05/17 09:00
MHDA- 2007/07/26 09:00
CRDT- 2007/05/17 09:00
PHST- 2007/05/17 09:00 [pubmed]
PHST- 2007/07/26 09:00 [medline]
PHST- 2007/05/17 09:00 [entrez]
AID - 10.2174/157340607780620671 [doi]
PST - ppublish
SO  - Med Chem. 2007 May;3(3):233-9. doi: 10.2174/157340607780620671.