Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway

Shan, Jianzhen; Xuan, Yanyan; Zheng, Shu; Dong, Qi; Zhang, Suzhan

doi:10.1631/jzus.b0920149

Cited by 96 publications

(55 citation statements)

References 17 publications

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“…Moreover, we also detected decreased apoptotic tumor cells by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay under hypoxia, which could be reversed by UA (data not shown). Additionally, inhibition of angiogenesis by UA was also confirmed by our current study and previous works (Shan et al, 2009;2011), which was also involved with HIF-1α accumulation. Therefore, UA could be a promising candidate to combine with current chemotherapy to reverse drug resistance and enhance tumor cell apoptosis under hypoxia.…”

Section: Discussionsupporting

confidence: 89%

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α

Shan

Xuan

Zhang

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To explore the efficacy of ursolic acid in sensitizing colon cancer cells to chemotherapy under hypoxia and its underlying mechanisms. Methods: Three colon cancer cell lines (RKO, LoVo, and SW480) were used as in vitro models. 5-Fluorouracil (5-FU) and oxaliplatin were used as chemotherapeutic drugs. Cell viability and apoptosis were tested to evaluate the sensitivity of colon cancer cells to chemotherapy. The transcription and expression levels of hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and vascular endothelial growth factors (VEGF) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting. Cycloheximide and MG132 were used to inhibit protein synthesis and degradation, respectively. In vitro tube formation assay was used to evaluate angiogenesis. Results: We demonstrated the chemosensitizing effects of ursolic acid with 5-FU and oxaliplatin in three colon cancer cell lines under hypoxia. This effect was correlated to its inhibition of MDR1 through HIF-1α. Moreover, ursolic acid was capable of inhibiting HIF-1α accumulation with little effects on its constitutional expression in normoxia. In addition, ursolic acid also down-regulated VEGF and inhibited tumor angiogenesis. Conclusions: Ursolic acid exerted chemosensitizing effects in colon cancer cells under hypoxia by inhibiting HIF-1α accumulation and the subsequent expression of the MDR1 and VEGF.

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Section: Discussionsupporting

confidence: 89%

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α

Shan

Xuan

Zhang

et al. 2016

J. Zhejiang Univ. Sci. B

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“…In addition, it is possible that these anticancer effects were due to the synergistic action of chlorogenic acid with other compounds such as ursolic acid and rutin [3,4], also present in YMT. It has been reported that ursolic induced apoptosis on HT-29 cells by suppressing EGFR/MAPK pathway [22], and rutin decreased by 1.2-fold the number of aberrant crypt foci in an azoxymethane-induced CRC in rats [23].…”

Section: Discussionmentioning

confidence: 97%

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of <i>Ilex laurina</i> and <i>Ilex paraguariensis</i> on Colon Cancer Cells

Pérez¹,

Maldonado²,

Rojano³

et al. 2014

Trop. J. Pharm Res

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“…A number of studies demonstrated that the MAPK pathway was aberrantly activated in CRC (Shan et al, 2009). The MEK5/ERK5 pathway is sequentially regulated by a series of upstream MAP kinase kinases (MEKs) in a signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Mitogen/Extracellular Signal-Regulated Kinase Kinase-5 Promoter Region Polymorphisms Affect the Risk of Sporadic Colorectal Cancer in a Southern Chinese Population

Diao

Wang²,

Zhang³

et al. 2012

DNA and Cell Biology

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Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case-control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C > T and rs3743354T > C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T > C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs] = 0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR = 0.79; 95% CI, 0.61-0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT + CC) was found in the smoker subgroup (adjusted OR = 0.63; 95% CI = 0.45-0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C > T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.

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Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway

Abstract: Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.

Cited by 96 publications

References 17 publications

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of <i>Ilex laurina</i> and <i>Ilex paraguariensis</i> on Colon Cancer Cells

Mitogen/Extracellular Signal-Regulated Kinase Kinase-5 Promoter Region Polymorphisms Affect the Risk of Sporadic Colorectal Cancer in a Southern Chinese Population

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