Retinol Inhibits the Invasion of Retinoic Acid–Resistant Colon Cancer Cells In Vitro and Decreases Matrix Metalloproteinase mRNA, Protein, and Activity Levels

Park, Eun Young; Wilder, Erik T.; Lane, Michelle A.

doi:10.1080/01635580701268238

Cited by 35 publications

(50 citation statements)

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“…35,36 In addition, retinol may also reduce matrix metalloproteinase mRNA, protein and activity levels. 37 The chemoprevention and therapeutic potential of retinoids was subsequently explored in some cancer types, with particular success in acute promyelocytic leukaemia. However, the benefits of retinoids therapy are dependent of cancer type and resistance of retinoids therapy is common.…”

Section: Discussionmentioning

confidence: 99%

“…A number of reports have indicated that retinol can alter gene transcription via different mechanisms. [34][35][36][37][38] In particular, 2 classes of nuclear receptors for retinoic acid, RAR and RXR, were implicated in the effects of retinol on in vivo. 34 These receptors form heterodimers to bind to specific retinoic-acid-response elements, and have various cell-type dependent effects on cell signaling pathways, apoptosis and cell cycle arrests.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Leung

Crozier

Talwar

et al. 2008

Intl Journal of Cancer

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Both the tumour growth and progression and the systemic inflammatory response have the potential to increase oxidative stress. We therefore examined the relationship between lipid-soluble antioxidant vitamins, lipid peroxidation, the systemic inflammatory response and survival in patients with primary operable (n 5 53) and advanced inoperable (n 5 53) colorectal cancer. Compared with those patients with primary operable colorectal cancer, patients with unresectable liver disease had significantly lower median concentrations of a-tocopherol (p < 0.001), lutein (p < 0.001), lycopene (p < 0.001), a-carotene (p < 0.01) and b-carotene (p < 0.001) and higher malondialdehyde concentrations. An elevated systemic inflammatory response (Glasgow prognostic score, mGPS) was associated with a greater proportion of females (p < 0.05) and more advanced tumour stage (p < 0.05), lower circulating levels of retinol (p < 0.01), lutein (p < 0.01), lycopene (p < 0.01) and a-(p < 0.01) and b-carotene but not MDA (p 5 0.633). In the liver metastases group 41 patients died of their cancer and a further 1 patient died of intercurrent disease on follow-up. On univariate survival analysis, mGPS (p < 0.01), retinol (p < 0.001), atocopherol (p < 0.05) and a-carotene (p < 0.05) were associated significantly with cancer-specific survival. On multivariate survival analysis of these significant variables, only mGPS (p < 0.01) and retinol (p < 0.001) were independently associated with cancer-specific survival. The results of the present study showed that the systemic inflammatory response was associated with a reduction of lipid-soluble antioxidant vitamins, whereas advanced tumour stage was associated with increased lipid peroxidation in patients with colorectal cancer. Of the antioxidant vitamins measured, only retinol was independently associated with cancer-specific survival. ' 2008 Wiley-Liss, Inc.Key words: colorectal cancer; vitamin A; vitamin E; carotenoids; malonyldialdehyde; TNM stage; Glasgow prognostic score; survival Colorectal cancer remains the second commonest cause of cancer deaths in Western Europe and North America. Each year in the United Kingdom, there are 35,000 new cases and 16,000 deaths attributable to the disease.1 Overall survival is poor; even in those patients who undergo potentially curative resection, more than one-third die within 5 years. It is increasingly recognised that variations in outcome in cancer patients are not solely determined by the characteristics of the tumour but also by host-immune response factors. [3][4][5] It is now accepted that the host systemic inflammatory response can be assessed by examining the changes in the circulating concentrations of acute-phase proteins, such as an elevated concentration of C-reactive protein and a low concentrations of albumin 6 and that these have prognostic values in patients with cancer. 7,8 Recently, the combination of C-reactive protein and albumin, known as the Glasgow prognostic score (GPS), has been validated as a prognostic factor in patients with color...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Leung

Crozier

Talwar

et al. 2008

Intl Journal of Cancer

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“…ATRA prevents tumor invasion in mice and inhibits in vitro invasion of colon cancer cells by down regulation of MMP-7 expression. Moreover, Park et al [200] reported that retinol reduces the invasive potential of retinoic acid resistance colon cancer cells by decreasing MMP-1,-2,-7,-9 expressions and activity. Retinol reduces the metastatic potential of colon cancer cells via down regulation of MMP induction in a retinoic acid receptor-independent mechanism.…”

Section: Other Promising Dietary Antioxidantsmentioning

confidence: 99%

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Verma

Kesh

Ganguly

et al. 2014

WJBC

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teinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/ anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows. AbstractThe process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-

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“…37) Previous studies have shown that retinol inhibits the growth and the invasion of RA-resistant colon cancer cells in vitro and in vivo. [19][20][21][22] Retinol reduces invasiveness by decreasing the activity and mRNA expression of matrix metalloprotease and phosphatidylinositol 3-kinase (PI3K) activity, and not through RAR/RXR pathways. In addition, we have shown that retinol may act in refractory cancer cells through mechanisms that are distinct from RAR/RXR.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21][22] In addition, we have shown that retinol is a potent suppressor of cancer cell growth and adhesion of several cancer cell lines including refractory cancers in vitro. 23) Retinol suppresses the growth of human gallbladder cancer NOZ C-1 cells to a greater extent than RA, while RP shows no effects.…”

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confidence: 99%

Effects of Pre- and Post-Administration of Vitamin A on the Growth of Refractory Cancers in Xenograft Mice

Imai

Yamasaki

et al. 2017

Biological & Pharmaceutical Bulletin

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Vitamin A is an essential nutrient that is obtained from the daily diet. The major forms of vitamin A in the body consist of retinol, retinal, retinoic acid (RA), and retinyl esters. Retinal is fundamental for vision and RA is used in clinical therapy of human acute promyelocytic leukemia. The actions of retinol and retinyl palmitate (RP) are not known well. Recently, we found that retinol is a potent anti-proliferative agent against human refractory cancers, including gallbladder cancer, being more effective than RA, while RP was inactive. In the current study, we determined serum retinol concentrations in xenograft mice bearing tumors derived from four refractory cancer cell lines. We also examined the effects of vitamin A on proliferation of human gallbladder cancer cells in vivo. Serum retinol concentrations were significantly lower in xenograft mice with tumors derived from various refractory cancer cell lines as compared with control mice. The growth of tumors was inhibited with increasing serum retinol concentrations obtained post-administration of RP. In addition, pre-administration of RP increased serum retinol concentrations and suppressed tumor growth. These results indicate that administration of RP can maintain retinol concentrations in the body and that this might suppress cancer cell growth and attachment. The regulation of vitamin A concentration in the body, which is critical biomarker of health, could be beneficial for cancer prevention and therapy.

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Retinol Inhibits the Invasion of Retinoic Acid–Resistant Colon Cancer Cells In Vitro and Decreases Matrix Metalloproteinase mRNA, Protein, and Activity Levels

Cited by 35 publications

References 43 publications

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Effects of Pre- and Post-Administration of Vitamin A on the Growth of Refractory Cancers in Xenograft Mice

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