Anti-Colon Carcinogenesis of Curcumin Analogs Combination With 5-Fluorouracil

Name: Khanitta Srimuangwong

keyword: Hexahydrocurcumin

LCSH: Colon -- (Anatomy) -- Cancer

; Curcumin analog

; Colorectal cancer, HT-29 cells

; combined treatment

Abstract: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer, but its chemo-resistance and toxicity limit the success to chemotherapy. A combination of 5-FU with natural substances is often used to enhance the efficacy and reduce the toxicity of this drug. Curcumin (CUR), a major pigment in turmeric, is widely used to prevent and treat a variety of cancers. CUR specifically inhibited mRNA and protein expression of cyclooxygenase-2 (COX-2), which highly expressed in a variety of human cancers, but did not suppressed the cyclooxygenase-1 (COX-1) that maintains body homeostasis. However, CUR was poor solubility and poor absorption which unsuitable for drug design. This study was performed to study the combining effects of 5-FU and hexahydrocurcumin (HHC), a major CUR metabolite on HT-29 colon cancer cell line and DMH-induced colon carcinogenesis in rats. The present study demonstrates that, in HT-29 cells, HHC significantly decreases cell viability and down-regulates the COX-2 mRNA expression compared to the control but does not alter the COX-1 mRNA. These results suggested that HHC may exert its anti-carcinogenesis by suppressing COX-2 mRNA expression. Furthermore, the combined effect of HHC with a low dose of 5-FU for 24 and 48 h of treatment were showed a quantitative synergistic inhibitory effect on growth of HT-29 cells. Moreover, this combined treatment significantly reduced the expression of COX-2 mRNA and protein and induced the apoptosis to a greater degree than 5-FU or HHC monotherapy. In the DMH-induced colorectal carcinogenesis of rats, HHC treatment alone markedly inhibited the formation of aberrant crypt foci (ACF), preneoplastic lesions in colorectal carcinogenesis as compared to a control group. It is reasonable to assume that HHC exerts growth inhibitory effect of colorectal carcinogenesis. Moreover, HHC in combination with 5-FU showed significantly reduced the ACF formation when compared either HHC or 5-FU treated alone. This combined treatment could decrease the level of COX-2 protein and induced apoptosis when compared to a vehicle group but dose not difference to 5-FU or HHC monotherapy. In addition, this combined treatment dose not alters the level of COX-1 protein. Therefore, the combination effects of these agents in inhibit the ACF formation may be exhibit through other mode of actions. The results from in vitro and in vivo studies illustrate that HHC is a specific COX-2 inhibitor that lack of toxicity and side effects to normal cells by did not alter the expression of COX-1 and no adverse effects on growth rate of colorectal cancer rat model and encouraging for further study the other mechanism and investigation in pre-clinical trial.

NARESUAN UNIVERSITY. NARESUAN UNIVERSITY LIBRARY

Address: PHITSANULOK

Email: library@nu.ac.th

Name: Jiraporn Tocharus

Role: Advisor

Name: Chainarong Tocharus

Role: Co-Advisor

Name: Pornpome Jintana

Role: Co-Advisor

Created: 2012

Modified: 2026-04-05

Issued: 2026-04-05

วิทยานิพนธ์/Thesis

application/pdf

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Anatomy

Grantor: Naresuan University

©copyrights Naresuan University

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