Matrix Metalloproteinase Inhibition as a Novel Anticancer Strategy: A Review with Special Focus on Batimastat and Marimastat

Rasmussen, Henrik; McCann, Peter P.

doi:10.1016/s0163-7258(97)00023-5

Cited by 368 publications

(228 citation statements)

References 24 publications

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“…In accordance with these results, quercetin and kaempferol markedly inhibited the caseinolytic activity of MMP-3 and inhibited breast cancer cell invasion, suggesting a relationship between the metastatic potential and MMP-3 activity. Indeed, batimastat (BB-94) and marimastat (BB-2516), two specific inhibitors of MMPs in clinical trials, have been found to reduce tumor metastasis [42] . Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG, inositol transferase), has been found to suppress the invasion of HSC-4 tongue carcinoma cells by reducing the gelatinolytic activities of pro-MMP-9 and pro-MMP-2 [43] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

et al. 2009

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IntroductionMetastatic invasion is the primary cause of patient mortality during breast cancer progression. For a transformed cell to metastasize to a distant site in the body, it must first lose adhesion, penetrate and invade the surrounding extracellular matrix (ECM), enter the vascular system, and adhere to distant organs [1] . The inhibition of invasion of cancer cells has been an important strategy in cancer treatment [2] . A crucial step in the invasive processes is the proteolytic degradation of the ECM and basal membranes [3] . Several studies have shown that among the enzymes responsible for ECM degradation, the matrix metalloproteinases (MMPs) appear to play a critical role [4][5][6] . MMPs are zinc-dependent endopeptidases, which collectively can degrade all constituents of the ECM. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, gelatinases, membrane-type MMPs and other MMPs [7] .Breast cancer is the major cause of malignancy-related deaths of women worldwide. In Thailand, breast cancer is the second most common cancer among women and its incidence is increasing [8] . Cancer invasion and metastasis are leading causes of morbidity and mortality in patients with breast cancer. Several studies have demonstrated that upregulation of MMP-1, -2, -3, -7, -9, -13, and -14 is associated with breast cancer cell invasion [9][10][11] .MMP-3, also designated stromelysin 1, is a member of the matrixin family, which plays a pivotal role in the degradation and remodeling of the ECM. MMP-3 degrades several components of the ECM, such as fi bronectin, laminin, collagen type IV [12][13][14] and proteoglycans, and is thought to play an important role in rheumatoid arthritis, osteoarthritis [15,16] , tumor cell invasion and metastasis [17] . Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, fl avonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their ability to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of fl avonoids on MDA-MB-231 cell invasion. Methods: The toxic concentration range of fl avonoids was evaluated using the MTT assay. The ability of MDA-MB-231 cells to invade was evaluated using a modifi ed Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confi rmed by ELISA. Results: Some putative fl avonoids, ie, quercetin and kaempferol (fl avonols), signifi cantly inhibited the in vitro invasion of MDA-MB-231 cells in a concentration-dependent manner, with IC 50 values of 27 and 30 μmol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC 50 values in the range of 30 μmol/L and 45 μmol/L, respectively. None of the fl avonoids had a signif...

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Section: Discussionmentioning

confidence: 99%

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

et al. 2009

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“…54) involved in the control of immune responses and of cell proliferation. This work also raises concerns about the side effects of those MPi currently undergoing clinical trials for the treatment of cancer, arthritis, and various forms of tissue injury (55)(56)(57). The potential role of MP in regulating responses to TNF family ligands suggests that such inhibition would have profound effects on immune responses and cell growth/survival.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Metalloproteinase Cleavage Enhances the Cytotoxicity of Fas Ligand

Knox

Milner

Green

et al. 2003

The Journal of Immunology

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The Fas ligand (FasL)/Fas receptor (CD95) pathway is an important mediator of apoptosis in the immune system and can also mediate cancer cell death. Soluble FasL (sFasL), shed from the membrane-bound form of the molecule by a putative metalloproteinase (MP), may function to locally regulate the activity of membrane-bound FasL. Using a replication-defective recombinant adenovirus-expressing FasL (RAdFasL), we identified a variable ability of different carcinoma cells to respond to FasL-induced cytotoxicity and to shed sFasL. Blockade of FasL cleavage with an MP inhibitor significantly enhanced RAdFasL-induced apoptosis suggesting that sFasL may antagonize the effect of membrane-bound FasL. In support of this concept, a recombinant adenovirus expressing a noncleavable form of FasL (RAdD4) was found to be a potent inducer of apoptosis even at very low virus doses. Our results highlight the therapeutic potential of noncleavable FasL as an antitumor agent and emphasize the important role of MP via the production of sFasL in regulating the response of the Fas pathway. Moreover, these findings have general implications for the therapeutic exploitation of TNF family ligands and for the possible impact of MP-based therapies on the normal physiology of Fas/TNF pathways.

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“…This activity may be necessary for the maintenance of the matrix in response to repeated microinjury; a change in the activity of several MMPs has also been associated with tendon rupture (10). Further evidence indicating the importance of MMPs in tendon has been provided by the side-effect profile of broad-spectrum MMP inhibitors such as marimastat, which has been shown to induce shoulder-and hand-tendon lesions (16). Whether these effects are mediated by inhibition of specific MMPs is not yet known, although related metalloenzymes may also be implicated.…”

Section: Discussionmentioning

confidence: 99%

Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells

Corps

Harrall

Curry

et al. 2002

Arthritis & Rheumatism

108

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Objective. To determine whether the fluoroquinolone antibiotic ciprofloxacin, which can cause tendon pain and rupture in a proportion of treated patients, affects the expression of matrix metalloproteinases (MMPs) in human tendon-derived cells in culture.Methods. Cell cultures were derived from 6 separate tendon explants, and were incubated in 6-well culture plates for 2 periods of 48 hours each, with ciprofloxacin (or DMSO in controls) and interleukin-1␤ (IL-1␤), alone and in combination. Samples of supernatant medium from the second 48-hour incubation were assayed for MMPs 1, 2, and 3 by Western blotting. RNA was extracted from the cells and assayed for MMP messenger RNA (mRNA) by semiquantitative reverse transcription-polymerase chain reaction, with normalization for GAPDH mRNA.Results. Unstimulated tendon cells expressed low or undetectable levels of MMP-1 and MMP-3, and substantial levels of MMP-2. IL-1␤ induced a substantial output of both MMP-1 and MMP-3 into cell supernatants, reflecting increases (typically 100-fold) in MMP mRNA, but had only minor effects on MMP-2 expression. Ciprofloxacin had no detectable effect on MMP output in unstimulated cells. Preincubation with ciprofloxacin potentiated IL-1␤-stimulated MMP-3 output, reflecting a similar effect on MMP-3 mRNA expression. Ciprofloxacin also potentiated IL-1␤-stimulated MMP-1 mRNA expression, but did not potentiate the output of MMP-1, and had no significant effects on MMP-2 mRNA expression or output.Conclusion. Ciprofloxacin can selectively enhance MMP expression in tendon-derived cells. Such effects might compromise tendon microstructure and integrity.

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Matrix Metalloproteinase Inhibition as a Novel Anticancer Strategy: A Review with Special Focus on Batimastat and Marimastat

Cited by 368 publications

References 24 publications

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

Inhibition of Metalloproteinase Cleavage Enhances the Cytotoxicity of Fas Ligand

Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells

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