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      Effects of Zanthoxylum acanthopodium on MMP-9 and GLUT-1 expression and histology changes in rats with cervical carcinoma

      , , , ,
      Pharmacia
      Pensoft Publishers

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          Abstract

          Cervical cancer is one of the most common cancers in Indonesia. It can be treated with molecular therapies targeting Matrix metallopeptidase 9 (MMP-9) and Glucose transporter (GLUT-1), which are enzymes that are involved in tumour cell invasion, metastasis and angiogenesis. Zanthoxylum acanthopodium (andaliman) is an Indonesian herb with anti-cancer properties. This study aimed to investigate the histological changes andaliman treatment caused in MMP-9 and GLUT-1 expression. This study used five groups of rats: control (C-), cancer model (C+), cancer-bearing rats with a 100-mg dose of Zanthoxylum acanthopodium methanol extract (ZAM)/BW (ZAM100), cancer-bearing rats with a 200-mg dose of ZAM /BW (ZAM200) and cancer-bearing rats with a 400-mg dose of ZAM/BW (ZAM400). Immunohistochemical methods were used to stain cervical tissue with MMP-9 and GLUT-1 antibodies, and a TUNEL assay was performed to investigate cell apoptosis. Zanthoxylum acanthopodium methanol extract administration did not affect rat body weight but had a significant effect on cervical cancer growth. There was an increase in MDA levels associated with SOD deficiency in tumour tissue. SOD activity increased due to ZAM administration, allowing cells to be protected from oxidant disruption and oxidative stress. ZAM ameliorated cervical carcinoma tissue damage and reduced the expression of MMP-9, GLUT-1 and apoptosis in serum and tissue (p < 0.01) In short, the higher the ZAM dose, the lower the expression of MMP-9, GLUT-1 and apoptosis, indicating that ZAM is effective to treat cervical cancer.

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          Most cited references35

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          Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview.

          Matrix metalloproteinases (MMPs) are zinc dependent proteolytic metalloenzyme. MMP-9 is one of the most complex forms of matrix metalloproteinases. MMP-9 has the ability to degrade the extracellular matrix (ECM) components and has important role in the pathophysiological functions. Overexpression and dysregulation of MMP-9 is associated with various diseases. Thus, regulation and inhibition of MMP-9 is an important therapeutic approach for combating various diseases including cancer. Inhibitors of MMP-9 can be used as anticancer agents. Till date no selective MMP-9 inhibitors passed the clinical trials. In this review the structure, activation, function and inhibitors of MMP-9 are mainly focused. Some highly active and/or selective MMP-9 inhibitors have been discussed which may be helpful to explore the structural significance of MMP-9 inhibitors. This study may be useful to design new potent and selective MMP-9 inhibitors against cancer in future.
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            Detection of apoptosis by TUNEL assay.

            Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay has been designed to detect apoptotic cells that undergo extensive DNA degradation during the late stages of apoptosis. The method is based on the ability of TdT to label blunt ends of double-stranded DNA breaks independent of a template. This chapter describes an assay for detection of apoptotic cells during mouse odontogenesis using a colorimetric TUNEL system.
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              A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential

              Implication By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. Background MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. Methods The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. Results MMP1, MMP9, MMP10, MMP11, and MMP13 were almost universally upregulated across all cancers, with significant (p   2) in ten of fifteen cancers. MMP3, MMP7, MMP12 and MMP14) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2, MMP7, MMP23B, MMP27 and MMP28) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. Conclusions Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5768-0) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Pharmacia
                PHAR
                Pensoft Publishers
                2603-557X
                0428-0296
                October 03 2022
                October 03 2022
                : 69
                : 4
                : 911-920
                Article
                10.3897/pharmacia.69.e89368
                d9fb9fbd-6e43-40dc-ba26-a9d03e4aa333
                © 2022

                http://creativecommons.org/licenses/by/4.0/

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