PMID- 17136318
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20151119
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 12
IP  - 1
DP  - 2007 Jan
TI  - Comparison of the rapid pro-apoptotic effect of trans-beta-nitrostyrenes with 
      delayed apoptosis induced by the standard agent 5-fluorouracil in colon cancer 
      cells.
PG  - 235-46
AB  - Trans-beta-nitrostyrene (TBNS) has been reported to be a potent inhibitor of 
      protein phosphatases PTB1 and PP2A and to display a pro-apoptotic effect even in 
      multidrug resistant tumour cells. Here we compared the anti-tumour potential of 
      TBNS with 5-fluorouracil (5-FU) as the standard chemotherapeutic agent for 
      colorectal cancer in LoVo cells. Resistance to 5-FU based therapy might be a 
      consequence of 5-FU's delayed effect requiring long-term effective concentrations 
      in the tumour tissue. Thus, alternatives like platin containing drugs with a more 
      rapid effect have been introduced recently. Compared to 5-FU TBNS displayed a 
      faster cytotoxic and pro-apoptotic effect. A 50% decrease in viability was 
      observed already after 8 h with TBNS while 5-FU displayed no significant effect 
      before 48 h. DNA fragmentation and caspase-3 assays confirmed the more rapid 
      apoptotic effect of TBNS. Since apoptosis affects individual cells these results 
      about a rapidly induced apoptosis were further studied on a single cell level in 
      microscopic assays of caspase-3 and caspase-8 activation. Adducts of 
      trans-beta-nitrostyrene displayed an anti-tumour effect comparable to TBNS which 
      suggests the possibility of creating adducts with optimised tissue targeting. 
      Finally, the calculation of a drug combination index displayed a synergistic 
      effect for the combination of TBNS and 5-FU in Lovo as well as in HT-29 and 
      HCT116 colon cancer cells.
FAU - Werner, Jens Martin
AU  - Werner JM
AD  - Institute of Pharmacology & Toxicology, University of Gottingen, Robert-Koch-Str. 
      40, D-37075, Gottingen, Germany.
FAU - Eger, Kurt
AU  - Eger K
FAU - Jurgen Steinfelder, Hans
AU  - Jurgen Steinfelder H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Styrenes)
RN  - 5287E3OUAV (beta-nitrostyrene)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*drug therapy/metabolism/*pathology
MH  - DNA Fragmentation/drug effects
MH  - Drug Resistance, Neoplasm
MH  - Enzyme Activation/drug effects
MH  - Fluorouracil/administration & dosage/*pharmacology
MH  - Humans
MH  - Styrenes/administration & dosage/*pharmacology
EDAT- 2006/12/01 09:00
MHDA- 2007/04/25 09:00
CRDT- 2006/12/01 09:00
PHST- 2006/12/01 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2006/12/01 09:00 [entrez]
AID - 10.1007/s10495-006-0530-x [doi]
PST - ppublish
SO  - Apoptosis. 2007 Jan;12(1):235-46. doi: 10.1007/s10495-006-0530-x.