scholarly journals Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising anti-cancer therapeutic

2018 ◽  
Author(s):  
Shiwanthi L Ranasinghe ◽  
Glen M Boyle ◽  
Katja Fischer ◽  
Jeremy Potriquet ◽  
Jason P Mulvenna ◽  
...  
Keyword(s):  
Cell Growth ◽  
Protease Inhibitor ◽  
Hydatid Cyst ◽  
Echinococcus Granulosus ◽  
Cancer Cell ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor

AbstractEgKI-1, a member of the Kunitz type protease inhibitor family, is highly expressed by the oncosphere of the canine tapeworm Echinococcus granulosus, the stage that is infectious to humans and ungulates, giving rise to a hydatid cyst localized to the liver and other organs. Larval protoscoleces, which develop within the hydatid cyst, have been shown to possess anti-cancer properties, although the precise molecules involved have not been identified. We show that recombinant EgKI-1 inhibits the growth and migration of a range of human cancers including breast, melanoma and cervical cancer cell lines in a dose-dependent manner in vitro without affecting normal cell growth. Furthermore, EgKI-1 treatment arrested the cancer cell growth by disrupting the cell cycle and induced apoptosis of cancer cells in vitro. An in vivo model of triple negative breast cancer (MDA-MB-231) in BALB/c nude mice showed significant tumor growth reduction in EgKI-1-treated mice compared with controls. These findings indicate that EgKI-1 shows promise for future development as an anti-cancer therapeutic.

scholarly journals Resveratrol Suppresses Ovarian Cancer Cell Growth and Invasion Through Upregulation of microRNA-34a

2020 ◽  
Author(s):  
Bing Wei ◽  
Shangli Yao ◽  
Ming Gao ◽  
Zujun Wang ◽  
Wenyan Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Molecular Mechanisms ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Anti Cancer ◽  
Underlying Mechanisms

Abstract Resveratrol (RES), a natural compound found in red wine, has previously reported to suppress ovarian cancer (OC) cell growth in vitro and in vivo; however, its potential molecular mechanisms are not fully elucidated. The aim of this study is to investigate the suppressive potential of RES in OC cell growth and invasion and reveal the underlying mechanisms. Herein, we found that RES treatment obviously suppressed the proliferative and invasive capacities of OC cells, and elevated cell apoptosis in vitro. Subsequent microarray and qRT-PCR analysis further showed that microRNA-34a (miR-34a) was significantly increased by RES treatment. Moreover, the inhibitory effects of RES on OC cells were enhanced by miR-34a overexpression, whereas weakened by miR-34a inhibition in OC cells. Of note, Bcl-2, an anti-apoptotic gene, was identified as a direct target of miR-34a. Then, we revealed that RES decreased the expression of Bcl-2 in OC cells in a dose dependent manner. Furthermore, the anti-tumor effects of RES were abolished by overexpression of Bcl-2 in OC cells. Overall, these results demonstrated that RES exerts the anti-cancer effects on OC cells through the miR-34a/Bcl-2 axis.

scholarly journals Downregulation of class II phosphoinositide 3-kinase PI3K-C2β delays cell division and potentiates the effect of docetaxel on cancer cell growth

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Ouma Cisse ◽  
Muzthahid Quraishi ◽  
Federico Gulluni ◽  
Federica Guffanti ◽  
Ioanna Mavrommati ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Hela Cells ◽  
Class Ii ◽  
Cancer Cell Growth ◽  
Clonogenic Assays ◽  
Anti Cancer ◽  
Pc3 Cells

Abstract Background Alteration of signalling pathways regulating cell cycle progression is a common feature of cancer cells. Several drugs targeting distinct phases of the cell cycle have been developed but the inability of many of them to discriminate between normal and cancer cells has strongly limited their clinical potential because of their reduced efficacy at the concentrations used to limit adverse side effects. Mechanisms of resistance have also been described, further affecting their efficacy. Identification of novel targets that can potentiate the effect of these drugs or overcome drug resistance can provide a useful strategy to exploit the anti-cancer properties of these agents to their fullest. Methods The class II PI3K isoform PI3K-C2β was downregulated in prostate cancer PC3 cells and cervical cancer HeLa cells using selective siRNAs and the effect on cell growth was determined in the absence or presence of the microtubule-stabilizing agent/anti-cancer drug docetaxel. Mitosis progression was monitored by time-lapse microscopy. Clonogenic assays were performed to determine the ability of PC3 and HeLa cells to form colonies upon PI3K-C2β downregulation in the absence or presence of docetaxel. Cell multi-nucleation was assessed by immunofluorescence. Tumour growth in vivo was assessed using a xenograft model of PC3 cells upon PI3K-C2β downregulation and in combination with docetaxel. Results Downregulation of PI3K-C2β delays mitosis progression in PC3 and HeLa cells, resulting in reduced ability to form colonies in clonogenic assays in vitro. Compared to control cells, PC3 cells lacking PI3K-C2β form smaller and more compact colonies in vitro and they form tumours more slowly in vivo in the first weeks after cells implant. Stable and transient PI3K-C2β downregulation potentiates the effect of low concentrations of docetaxel on cancer cell growth. Combination of PI3K-C2β downregulation and docetaxel almost completely prevents colonies formation in clonogenic assays in vitro and strongly inhibits tumour growth in vivo. Conclusions These data reveal a novel role for the class II PI3K PI3K-C2β during mitosis progression. Furthermore, data indicate that blockade of PI3K-C2β might represent a novel strategy to potentiate the effect of docetaxel on cancer cell growth.

scholarly journals Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0200433 ◽  
Author(s):  
Shiwanthi L. Ranasinghe ◽  
Glen M. Boyle ◽  
Katja Fischer ◽  
Jeremy Potriquet ◽  
Jason P. Mulvenna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protease Inhibitor ◽  
Echinococcus Granulosus ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor

Members of the Kunitz-type protease inhibitor gene family of potato inhibit soluble tuber invertase in vitro

2002 ◽  
Vol 45 (2-4) ◽  
pp. 163-176 ◽  
Author(s):  
Heike Glaczinski ◽  
A. Heibges ◽  
F. Salamini ◽  
Christiane Gebhardt
Keyword(s):  
Protease Inhibitor ◽  
Gene Family ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor ◽  
Inhibitor Gene

scholarly journals Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shiwanthi L. Ranasinghe ◽  
Vanessa Rivera ◽  
Glen M. Boyle ◽  
Donald P. McManus
Keyword(s):  
Tumor Microenvironment ◽  
Protease Inhibitor ◽  
Survivin Expression ◽  
Surrounding Tissue ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Anti Cancer ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor

Abstract Modulating the tumor microenvironment to promote an effective immune response is critical in managing any type of tumor. Melanoma is an aggressive skin cancer and the incidence rate is increasing worldwide. Potent protease inhibitors have recently been extensively researched as potential therapeutic agents against various cancers. EgKI-1 is a potent Kunitz type protease inhibitor identified from the canine tapeworm Echinococcus granulosus that has shown anti-cancer activities in vivo. In this study we show that EgKI-1 significantly reduced the growth of melanoma in the B16-F0 mouse model and was not toxic to normal surrounding tissue. Moreover, EgKI-1 treatment significantly reduced survivin expression levels and increased the CD8+ T cell population in draining axillary lymph nodes. Therefore, EgKI-1 potentially reduces tumor growth by inducing apoptosis and modulating the tumor microenvironment, and has potential for development as an intra-lesional treatment for melanoma.

scholarly journals Joannsin, a novel Kunitz-type FXa inhibitor from the venom of Prospirobolus joannsi

2017 ◽  
Vol 117 (06) ◽  
pp. 1031-1039 ◽  
Author(s):  
Ning Luan ◽  
Chunling Zhou ◽  
Pengpeng Li ◽  
Rose Ombati ◽  
Xiuwen Yan ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Factor Xa ◽  
Potential Candidate ◽  
Amino Acid Residues ◽  
Secretory Glands ◽  
Fxa Inhibitor ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor

SummaryThe repugnatorial glands of millipedes release various defensive chemical secretions. Although varieties of such defensive secretions have been studied, none of them is protein or peptide. Herein, a novel factor Xa (FXa) inhibitor named joannsin was identified and characterised from repugnatorial glands of Prospirobolus joannsi. Joannsin is composed of 72 amino acid residues including six cysteines, which form three intra-molecular disulfide bridges. It is a member of Kunitz-type protease inhibitor family, members of which are also found in the secretory glands of other arthropods. Recombinant joannsin exhibited remarkable inhibitory activity against trypsin and FXa with a Ki of 182.7 ± 14.6 and 29.5 ± 4.7 nM, respectively. Joannsin showed strong anti-thrombosis functions in vitro and in vivo. Joannsin is the first peptide component in millipede repugnatorial glands to be identified and is a potential candidate and/or template for the development of anti-thrombotic agents. These results also indicated that there is Kunitz-type protease inhibitor toxin in millipede repugnatorial glands as in other arthropods secretory glands.

scholarly journals Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4608 ◽  
Author(s):  
Xiao-Fan Huang ◽  
Kai-Fu Chang ◽  
Shan-Chih Lee ◽  
Gwo-Tarng Sheu ◽  
Chia-Yu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Tumor Cell ◽  
Dependent Manner ◽  
Tumor Cell Growth ◽  
Normal Cells ◽  
Cedrus Atlantica ◽  
Anti Cancer

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

scholarly journals Targeting secretory leukocyte protease inhibitor (SLPI) inhibits colorectal cancer cell growth, migration and invasion via downregulation of AKT

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9400 ◽  
Author(s):  
Zhijiang Wei ◽  
Guiying Liu ◽  
Rufu Jia ◽  
Wei Zhang ◽  
Li Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Protease Inhibitor ◽  
Cancer Cell ◽  
Mrna Level ◽  
Akt Signaling ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Migration And Invasion ◽  
Cancer Cell Growth

The secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor which plays important role in bacterial infection, inflammation, wound healing and epithelial proliferation. Dysregulation of SLPI has been reported in a variety of human cancers including glioblastoma, lung, breast, ovarian and colorectal carcinomas and is associated with tumor aggressiveness and metastatic potential. However, the pathogenic role of SLPI in colorectal cancer is still unclear. Here we showed that SLPI mRNA level was significantly upregulated in colorectal cancer tissues compared to adjacent normal controls. Targeting SLPI by siRNA inhibited proliferation, migration and invasion of colorectal cancer cells lines HT29 and HT116 in vitro. Mechanistically, blockage of cancer cell growth and metastasis after SLPI knockdown was associated with down-regulation of AKT signaling. In conclusion, SLPI regulated colorectal cell growth and metastasis via AKT signaling. SLPI may be a novel biomarker and therapeutic target for colorectal cancer. Targeting AKT signaling may be effective for colorectal cancer treatment.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth
Sign in / Sign up

Export Citation Format

Share Document