Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Abstract

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-

Aurora-A modulates MMP-2 expression via AKT/NF-κB pathway in esophageal squamous cell carcinoma cells

“…An increased expression of MMP-2 has frequently been detected in solid tumors, which can contribute to cancer invasion and metastasis through the degradation of ECM, which facilitates and accelerates the tumor cells to invade new tissues and enter the blood stream to travel to distant sites [2][3][4][5][6][7]. In this study, we found that MMP-2 was overexpressed in ESCC, which was consistent with previous studies [5,6].…”

“…The degradation of basement membranes and stromal extracellular matrix (ECM) by expressing and secreting various proteolytic enzymes plays a critical role in promoting tumor invasion and metastasis. The matrix metalloproteinases 2 (MMP-2, gelatinase A, 72 kDa), a member of the human zinc-dependent endopeptidase family, efficiently degrades components of the basement membrane and ECM such as Type IV collagen and fibronectin, and contributes to the invasion and metastasis of cancer cells [2][3][4]. Earlier reports have indicated that the increased expression level of MMP-2 is correlated with the invasive properties of various malignant tumors including ESCC [5][6][7], indicating that MMP-2 plays an important role in regulating malignant development of tumor cells.…”

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

“…The process of metastasis involves several steps, including the detachment of cancer cells from the primary tumour, followed by the migration, adhesion and invasion of cancer cells into blood or lymphatic vessels; cancer cells then undergo extravasation and subsequently interact with target tissues, where they form metastastic foci in distant organs (41). The destruction of the extracellular matrix (ECM) by enzymes is an essential initial step in the processes of tumor cell invasion and metastasis, and several studies have reported that, among the enzymes responsible for ECM degradation, MMPs are have a critical role (42,43).…”

Can Capsaicin Present in Food Act as Carcinogenic, Antitumor or Both

“…In this regard, it is noted that tumor cells may die by the same systems they require to emerge and develop. The quantitative difference between oxidative stress in cancer and normal cells was related to liver cells [78], leukemia cells [79], breast cells [80] and gastrointestinal cancer [81].…”