Neoplasma Vol.51, p.460-464, 2004
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| Title: Acetaminophen and DMSO modulate growth and gemcitabine
cytotoxicity in FM3A breast cancer cells in vitro
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| Author: A., BILIR
; A.D., GUNERI
; M.A., ALTINOZ
; |
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Abstract: Addition of antioxidants to chemotherapy is an unresolved problem
in oncology. It is still an issue of debate, whether antioxidants
may reduce rough cellular toxicity and thereby the systemic side
effects of the chemotherapy, without sacrificing the anti-tumor
efficacy.
Gemcitabine is a rather new anti-cancer agent, which is quite
potent against a range of drug resistant tumors, particularly
breast cancer. Tumor-sensitivity towards gemcitabine can be
increased with COX inhibitory anti-inflammatory agents and
ribonucleotide reductase (RR) inhibitor flavopiridol.
Acetaminophen and DMSO are two unique anti-inflammatory and anti-
oxidant agents with unrelated structures, yet both capable to
block RR and COX, simultaneously. Using plating efficacy and 3H-
thymidine labeling, we monitored efficacy of acetaminophen and
DMSO to modulate growth and gemcitabine sensitivity in FM3A breast
tumor cells, which is highly used to study thymineless death
induced by nucleotide-metabolism hemming drugs. Peculiarly,
acetaminophen alone stimulated S-phase, which was not accompanied
with enhanced plating, rather resulting in 40.3% growth inhibition
at the 96 hour. DMSO alone significantly diminished both the
plating and S-phase, which resulted in 71.7% growth inhibition at
the 96 hour. Gemcitabine drastically reduced S-phase and plating
until 72 hours, yet at 96 hours it lost its efficacy to suppress
the S-phase with concomitant 2-fold rise in cell numbers in
comparison to 72 hour time point. Both DMSO and acetaminophen
brought S-phase to around zero percent in combination with
gemcitabine until 48 hours, yet they both reduced early
cytotoxicity of gemcitabine at the same time interval. However, at
the 96 hour, they both strongly augmented gemcitabine efficacy to
block S-phase and prevented the rise in plating. Acetaminophen and
DMSO should be tested in animal models, whether they could augment
efficacy and reduce the toxicity of gemcitabine.
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| Keywords: acetaminophen, DMSO, gemcitabine, breast cancer, FM3A
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| Year: 2004, Volume: 51, Issue: |
Page From: 460, Page To: 464 |
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Price:
12.00 €
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