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Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells.

Abstract：

AIM:To investigate the ability of hexahydrocurcumin (HHC) to enhance 5-fluorouracil (5-FU) in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase (COX)-2 expression. METHODS:Antiproliferative effects of HHC and 5-FU, alone and in combination, on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide (MTT) reduction assay. In combination treatment, low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxicity and side effects of 5-FU. The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. RESULTS:MTT reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control. Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor. This finding was supported by the observation that HHC significantly down-regulates COX-2 mRNA expression compared to the control (control: 100.05% ± 0.03% vs HHC: 61.01% ± 0.35%, P < 0.05) but does not alter COX-1 mRNA. In combined treatment, addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy. Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 μmol/L in combination with HHC at the concentration of 25 μmol/L significantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone (HHC + 5-FU: 31.93% ± 5.69%, 5-FU: 100.66% ± 4.52% vs HHC: 61.01% ± 0.35%, P < 0.05). CONCLUSION:HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.

journal_name

World J Gastroenterol

journal_title

World journal of gastroenterology

authors

Srimuangwong K,Tocharus C,Yoysungnoen Chintana P,Suksamrarn A,Tocharus J

doi

10.3748/wjg.v18.i19.2383

subject

Has Abstract

pub_date

2012-05-21 00:00:00

pages

2383-9

issue

eissn

1007-9327

issn

2219-2840

journal_volume

pub_type

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Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells.