Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

Badr, Gamal; Sayed, Douaa; Maximous, Doaa; Mohamed, Amany O.; Gül, Mustafa

doi:10.1159/000366366

Cited by 20 publications

(10 citation statements)

References 37 publications

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“…SVT inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. Moreover, SVT sensitized the primary breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide [ 60 ]. In our recent study, the anti-cancer effect of SVT in cervical cancer via increase of death receptor 3 and 5 and inactivation of NF-κB was demonstrated [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression

et al. 2015

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Snake venom toxin (SVT) from Vipera lebetina turanica contains a mixture of different enzymes and proteins. Peroxiredoxin 6 (PRDX6) is known to be a stimulator of lung cancer cell growth. PRDX6 is a member of peroxidases, and has calcium-independent phospholipase A2 (iPLA2) activities. PRDX6 has an AP-1 binding site in its promoter region of the gene. Since AP-1 is implicated in tumor growth and PRDX6 expression, in the present study, we investigated whether SVT inhibits PRDX6, thereby preventing human lung cancer cell growth (A549 and NCI-H460) through inactivation of AP-1. A docking model study and pull down assay showed that SVT completely fits on the basic leucine zipper (bZIP) region of c-Fos of AP-1. SVT (0–10 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decreased cIAP and Bcl2 expression via inactivation of AP-1. In an xenograft in vivo model, SVT (0.5 mg/kg and 1 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression, but increased expression of proapoptotic proteins. These data indicate that SVT inhibits tumor growth via inhibition of PRDX6 activity through interaction with its transcription factor AP-1.

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Section: Discussionmentioning

confidence: 99%

Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression

et al. 2015

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“…An extensive development and conjugation of drug delivery systems with some snake toxins, which has reduced the toxicity and improved the selectivity toward cancer cells [ 96 , 97 ], highlight their promising applications as direct anti-cancer agents or potential tools for the development of novel therapeutic strategies [ 16 ]. Finally, the in vivo validation of anti-metastatic effect described on in vitro cancer cell lines is a pending issue for drug discovery from snake toxins.…”

Section: Discussionmentioning

confidence: 99%

Targeting Metastasis with Snake Toxins: Molecular Mechanisms

Urra

Araya‐Maturana

2017

Toxins

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Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network.

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“…Apoptosis occurs through both extrinsic (Fas) and the intrinsic (mitochondrial) pathways [ 29 ]. The mitochondria-mediated pathway involves a cascade of events, including the efflux of cytochrome C, the formation of apoptosomes accompanied with Apaf-1 and caspase-9, resulting in caspase-3 activation and subsequent induction of apoptosis [ 30 ]. Mitochondria-mediated apoptosis had been observed in response to several metal nanoparticles, such as copper oxide nanoparticles, silver nanoparticles and zinc oxide nanoparticles [ 31 – 33 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial-Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles

Zou

Jiang

et al. 2016

PLoS ONE

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The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose- and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations.

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Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

Cited by 20 publications

References 37 publications

Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression

Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression

Targeting Metastasis with Snake Toxins: Molecular Mechanisms

DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial-Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles

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