Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities

Suzuki, Izuru; Iigo, Masaaki; Ishikawa, Chikako; Kuhara, Tetsuya; Asamoto, Makoto; Kunimoto, Takehiko; Moore, Malcolm A; Yazawa, Kazunaga; Araki, Eiji; Tsuda, Hiroyuki

doi:10.1002/(sici)1097-0215(19971114)73:4<607::aid-ijc24>3.0.co;2-4

Cited by 79 publications

(45 citation statements)

References 19 publications

(27 reference statements)

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“…Targeted gene disruption of gelatinase B suppressed development of abdominal aortic aneurysms in mice (49), emphasizing the role of this MMP in such a degenerative condition associated with aging and atherosclerosis. The gelatinase inhibition by fatty acids as we have disclosed in an in vitro study and then confirmed in an ex vivo model on human skin tissue (32) could thus explain, at least partly, the relationship between a Mediterranean-style diet, in which olive oil is the main source of fat, and protection from cardiovascular disease (50); it could also be involved in the reduction of lung metastasis formation by colon carcinoma cells in athymic mice after treatment by oleic acid (22).…”

Section: Effect Of Elaidic Acid On the Degradation Of Human Skin Collmentioning

confidence: 77%

“…They bind to serine proteinases such as neutrophil elastase (18,19) and plasmin (20,21) and modulate their catalytic activities. Studies by Suzuki et al (22) show that oleic acid, 18-carbon fatty acid with one double carbon bond in the cis position, partially inhibits the formation of lung metastases from subcutaneous implantation of colon carcinoma cells in athymic mice. We recently reported that oleic acid inhibited in a dose-dependent manner the hydrolysis of the fluorogenic substrate Mca-L-Pro-Leu-Gly-Leu-Dpa-AlaArg-NH 2 (23) by gelatinase A (24,25).…”

Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

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Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

Berton

Rigot

Huet

et al. 2001

Journal of Biological Chemistry

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The matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9) are implicated in the physiological and pathological breakdown of several extracellular matrix proteins. In the present study, we show that long-chain fatty acids (e.g. oleic acid, elaidic acid, and cis-and trans-parinaric acids) inhibit gelatinase A as well as gelatinase B with K i values in the micromolar range but had only weak inhibitory effect on collagenase-1 (MMP-1), as assessed using synthetic or natural substrates. The inhibition of gelatinases depended on fatty acid chain length (with C18 > C16, C14, and C10), and the presence of unsaturations increased their inhibitory capacity on both types of gelatinase. Ex vivo experiments on human skin tissue sections have shown that micromolar concentrations of a long-chain unsaturated fatty acid (elaidic acid) protect collagen and elastin fibers against degradation by gelatinases A and B, respectively. In order to understand why gelatinases are more susceptible than collagenase-1 to inhibition by longchain fatty acids, the possible role of the fibronectin-like domain (a domain unique to gelatinases) in binding inhibitory fatty acids was investigated. Affinity and kinetic studies with a recombinant fibronectin-like domain of gelatinase A and with a recombinant mutant of gelatinase A from which this domain had been deleted pointed to an interaction of long-chain fatty acids with the fibronectin-like domain of the protease. Surface plasmon resonance studies on the interaction of longchain fatty acids with the three individual type II modules of the fibronectin-like domain of gelatinase A revealed that the first type II module is primarily responsible for binding these compounds. Matrix metalloproteinases (MMPs)1 compose a family of at least 23 related zinc-dependent endopeptidases (1) that are collectively able to degrade extracellular matrix proteins such as collagens, laminins, fibronectin, elastin, and proteoglycans. They are consequently implicated in physiological remodeling of connective tissue occurring in embryonic development and repair (2-4). Most of them are secreted as inactive proenzymes and are then extra-or pericellularly activated by other MMPs or serine proteinases (5). Their catalytic activities are strictly controlled by endogenous specific inhibitors designated as tissue inhibitors of metalloproteinases (TIMPs) (6) and also ␣ 2 -macroglobulin (7). The balance between activated MMPs and TIMPs determines the overall MMP proteolytic activity and consequently the extent of extracellular matrix degradation. Local disruption of the MMP-TIMP balance can lead to pathological degradative processes including rheumatoid arthritis, atherosclerosis, tumor growth, and metastasis (8 -10). MMPs are multidomain enzymes containing propeptide, catalytic and, except matrilysin (MMP-7), MMP-23, and endometase/matrilysin-2 (MMP-26), hemopexin-like domains. Gelatinase A (MMP-2) and gelatinase B (MMP-9) contain in addition three tandem copies of a 58-amino acid fibronectin type II (FN-II) modul...

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Section: Effect Of Elaidic Acid On the Degradation Of Human Skin Collmentioning

confidence: 77%

Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

Berton

Rigot

Huet

et al. 2001

Journal of Biological Chemistry

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“…This activity may be related to changes in the fatty acid composition of tumour cells, which impaired the tumour cell membrane and reduced the ability to metastasize 109 . Moreover, impaired attachment to endothelial cells and the indicated decrease in metalloproteinase-9 activity in tumour cells may play a role in these effects 110 . Some results from in vivo experiments confirm the importance of the antiangiogenic activity of DHA (ref.…”

Section: Antimetastatic and Antiangiogenic Activity Of Dhamentioning

confidence: 99%

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Skender¹,

Vaculová²,

Hofmanová³

2012

BIOMED PAP

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Background. Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment. Results. From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family. Conclusion. Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

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“…Conversely, treatment with linoleic acid and arachidonic acid, two n-6 PUFAs, had no effect on EZH2 expression, confirming previous reports that suggest the beneficial effects of fatty acids on metastasis are specific for n-3 PUFAs, while n-6 PUFAs are associated with increased risk of metastasis (Bartsch et al, 1999;Chen et al, 2007;Hubbard & Erickson, 1987). DHA and EPA were also shown to inhibit expression of MMP-2 and MMP-9 (Suzuki et al, 1997). Fish oil as well as the individual DHA and EPA components have also been reported to have inhibitory effects on NFκB signalling in both cancer-related and non-cancer-related pathways, suggesting that decreases in the pro-metastatic proteins may all be related to NFκB (Fickl et al, 2005;Ghosh-Choudhury et al, 2009;Schley et al, 2005;Weise et al,).…”

Section: Fish Oilmentioning

confidence: 99%

The Beneficial Effects of Nutritional Compounds on Breast Cancer Metastasis

Altenburg¹,

Siddiqui²

2011

Breast Cancer - Current and Alternative Therapeutic Modalities

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Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities

Cited by 79 publications

References 19 publications

Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

The Beneficial Effects of Nutritional Compounds on Breast Cancer Metastasis

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