Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) – experimental validation in human breast and colon cancer

Kothapalli, Roopa; Siveen, Kodappully Sivaraman; Tan, Tuan Zea; Thiery, Jean Paul; Kumar, Alan Prem; Sethi, Gautam; Swaminathan, Kunchithapadam

doi:10.1080/09168451.2016.1200456

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…According to substrate specificity, sequence similarity, and domain organization, vertebrate MMPs are classified as collagenases (MMP‐1, ‐8, ‐13, ‐18), gelatinases ((MMP‐2, MMP‐9), stromelysins (MMP‐3, MMP‐10), matrilysins (MMP‐7, MMP‐26), membrane‐type MMPs (MMP‐14, ‐15, ‐16, ‐24, and MMP‐17, ‐25), and others (MMP‐12, ‐19, ‐20, ‐21, ‐23, ‐27, ‐28) . All MMPs contain a catalytic zinc‐binding motif, a linker region that links the catalytic domain region with the C‐terminal hemopexin (Hpx) domain, an N‐terminal signal sequence domain for secretion, a pro‐peptide region to maintain the latency for cell signaling . MMP‐13, also known as collagenase‐3, is secreted as an inactive pro‐form.…”

Section: Introductionmentioning

confidence: 99%

Recent Research Advances in Selective Matrix Metalloproteinase‐13 Inhibitors as Anti‐Osteoarthritis Agents

2017

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Matrix metalloproteinase-13 (MMP-13) plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). The subtle differences between the S1' loop of MMP-13 and that of other MMPs offer a structural base for the design of selective MMP-13 inhibitors to mitigate the unperceived risk associated with inhibiting other MMP isoforms. In this review, we summarize zinc-binding and non-zinc-binding selective MMP-13 inhibitors. The zinc-binding MMP-13 inhibitors contain a small set of zinc-binding groups (ZBGs), including hydroxamic acid, pyrimidinetrione, reversed hydroxamic acid and hydantoin, carboxylic acid, 1,2,4,-triazole, and 1,2,4,-triazolone. The non-zinc-binding MMP-13 inhibitors have different structural scaffolds, including diphenyl ethers, biaryls (aryltetrazoliums, arylfurans, pyrazole-indoles), pyrimidines, and aryl/cycloalkyl-fused pyrimidines. This review provides a systematic overview of recent developments in MMP-13 inhibitors for the treatment of OA, with emphasis on their enzyme inhibitory potency, selectivity, and biological activities, and highlights the various binding modes of typical inhibitors with MMP-13.

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Section: Introductionmentioning

confidence: 99%

Recent Research Advances in Selective Matrix Metalloproteinase‐13 Inhibitors as Anti‐Osteoarthritis Agents

2017

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“…In addition to EMT, matrix metalloproteinases (MMPs) are also involved in increasing cancer metastasis [207][208][209][210][211], and recent experiments have confirmed this. MMP-2 induces EMT to increase squamous cell carcinoma metastasis, and it may act as an independent factor in patient prognosis [212].…”

Section: Exosomes and Tumor Metastasismentioning

confidence: 98%

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

et al. 2022

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Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract

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“…[164][165][166] According to literature, various in vitro and in vivo models showed that natural bioactive compounds, including those from G. glabra, have antimetastasis potential 167 including Matrix metalloproteinases (MMPs), such as MMP-2, and MMP-9, and urokinase plasminogen activator (uPA) play a significant role in the metastasis process by degrading extracellular matrix (ECM) of cancerous cells as well as modulating the mechanism of angiogenesis in the maintenance of tumor cell survivability. 168,169 MMPs are degradation enzymes that modulate numerous physiological processes, such as cell growth, differentiation and apoptosis. However, overexpression of MMP-2 and MMP-9 is linked with prooncogenic events, such as neoangiogenesis, tumor cell proliferation, and metastasis.…”

Section: Antimetastic Activitiesmentioning

confidence: 99%

Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects

Tuli¹,

Garg²,

Mehta³

et al. 2022

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Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice ( Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.

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Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) – experimental validation in human breast and colon cancer

Cited by 7 publications

References 41 publications

Recent Research Advances in Selective Matrix Metalloproteinase‐13 Inhibitors as Anti‐Osteoarthritis Agents

Recent Research Advances in Selective Matrix Metalloproteinase‐13 Inhibitors as Anti‐Osteoarthritis Agents

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects

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