scholarly journals Spider Toxin Peptide-Induced NIR Gold Nanocluster Fabrication for GSH-Responsive Cancer Cell Imaging and Nuclei Translocation

Author(s):  
Huaxin Tan ◽  
Sisi Liu ◽  
Yaolin He ◽  
Guofeng Cheng ◽  
Yu Zhang ◽  
...  

Goldnanoclusters (GNCs) have become a promising nanomaterial for bioimaging because of their unique optical properties and biocompatibility. In this study, lycosin-I peptide, which possesses a highly selective anticancer activity by affecting the permeability of cancer cell membrane, was firstly modified for constructing fluorescent GNCs (LGNCs) for bioimaging of tumor cells. The obtained LGNCs exhibited strong near-infrared (NIR) fluorescence, which can be further enhanced by the peptide-induced aggregation and selectively stained three cancerous cell lines over normal cell lines with low intrinsic toxicity. After uptake by tumor cells, LGNC aggregates can be depolymerized into ultrasmall nanoclusters by high-level glutathione (GSH) and realize the nuclear targeting translocation. Collectively, our work suggests the potential of natural active biomolecules in designing NIR fluorescent GNCs for bioimaging.

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 641
Author(s):  
Kaitlin M. Branch ◽  
Erica C. Garcia ◽  
Yin Maggie Chen ◽  
Matthew McGregor ◽  
Mikayla Min ◽  
...  

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 683
Author(s):  
Giorgia Simonetti ◽  
Carla Boga ◽  
Joseph Durante ◽  
Gabriele Micheletti ◽  
Dario Telese ◽  
...  

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 μM). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 µM) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 µM).


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3292
Author(s):  
Mari Palviainen ◽  
Kirsi Laukkanen ◽  
Zeynep Tavukcuoglu ◽  
Vidya Velagapudi ◽  
Olli Kärkkäinen ◽  
...  

Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.


2018 ◽  
Vol 2 (S1) ◽  
pp. 36-37
Author(s):  
Nicolas Seranio ◽  
Louise Aguarin ◽  
Jay F. Dorsey ◽  
John P. Christodouleas ◽  
Gary D. Kao

OBJECTIVES/SPECIFIC AIMS: Bladder cancer patients being considered for immune checkpoint blockade are often judged on immunohistochemical staining for the checkpoint target protein PD-L1 in the original surgery or biopsy sample. However, sampling error or the clinical evolution of most patients’ cancer can render the original PD-L1 assessment no longer accurate. In contrast, circulating tumor cells (CTCs) allow serial noninvasive sampling of the current tumor status throughout a patient’s clinical course including those with the highest metastatic potential. We therefore sought to develop a method for quantifying PD-L1 expression in CTCs towards addressing inherent limitations of current UC management. METHODS/STUDY POPULATION: This work utilizes both cancer cell lines as well as patient samples. Positive and negative control cancer cell lines were assessed via “industry standard” antibodies for PD-L1 expression via Western blots and immunofluorescence, and a threshold-based method was developed for reliable quantification. PDL-1 expression was additionally verified via interferon-mediated up-regulation. CTCs isolated from bladder cancer patient samples via a density centrifugation method were then assessed for PD-L1 via the same antibodies. RESULTS/ANTICIPATED RESULTS: We will show preliminary preclinical and clinical data that validates the sensitivity and specificity of our assay. A case study will be presented that illustrate the potential useful of the novel approach we describe and which should be complementary to current clinical practices. In a patient with metastatic bladder cancer, this method effectively detected the PD-L1 expression in CTCs taken at a time coincident to when the patient derived an excellent response to the PD-L1 checkpoint inhibitor Pembrolizumab. DISCUSSION/SIGNIFICANCE OF IMPACT: This work highlights the potential utility of CTCs in the management of bladder cancer. It may be the case that this assay in conjunction with current methods of patient selection for immunotherapy may allow for better response prediction than either method alone.


Author(s):  
Behshad Eskandari ◽  
Maliheh Safavi ◽  
Seyede Nargess Sadati Lamardi ◽  
Mahdi Vazirian

Nowadays, cancer is the second prevalent cause of mortality after cardiovascular diseases in developed and the third one in developing countries. Adverse effects of chemotherapeutic agents bring the necessity of investigating about new medications with fewer side effects. Daphne L. genus is one of the natural sources with valuable reported anticancer effects. This study aimed to assess the cytotoxic effect of some extracts from the aerial parts of Daphne pontica collected from North of Iran on cancer cell lines.Extraction of the plant material was performed by maceration (3×72 h) of 200 g of sample with petroleum ether, chloroform, ethyl acetate, and methanol, respectively. The total extract was also obtained by maceration of the sample with 80% ethanol. Different concentrations of the dried extracts were prepared to assess their cytotoxic effect by 24 h incubation of cell lines with different extracts and then MTT (dimethyl thiazolyl diphenyl tetrazolium) assay on three cancerous cell lines (MDA-MB-231, MCF-7 and T47D), performed in triplicate. IC50 was then estimated from curves constructed by plotting cell survival (%) versus sample concentration (µg/ml). Results indicated that ethyl acetate fraction of D. pontica had the most potent cytotoxic effect in MTT assay with IC50 = 977.46 µg/ml; while other fractions were weaker in toxicity (IC50>1000 µg/ml). By comparing to potent cytotoxic effects of other Daphne species, it seems that the cytotoxic properties of D. pontica is different from other species of this genus since according to this study, no significant antineoplastic properties against the three breast cancer cell lines were determined. Further studies on other pharmacological activities of this plant are recommended.


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