scholarly journals Flavylium-Based Hypoxia-Responsive Probe for Cancer Cell Imaging

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4938
Author(s):  
Thitima Pewklang ◽  
Sirawit Wet-osot ◽  
Sirilak Wangngae ◽  
Utumporn Ngivprom ◽  
Kantapat Chansaenpak ◽  
...  

A hypoxia-responsive probe based on a flavylium dye containing an azo group (AZO-Flav) was synthesized to detect hypoxic conditions via a reductase-catalyzed reaction in cancer cells. In in vitro enzymatic investigation, the azo group of AZO-Flav was reduced by a reductase in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) followed by fragmentation to generate a fluorescent molecule, Flav-NH2. The response of AZO-Flav to the reductase was as fast as 2 min with a limit of detection (LOD) of 0.4 μM. Moreover, AZO-Flav displayed high enzyme specificity even in the presence of high concentrations of biological interferences, such as reducing agents and biothiols. Therefore, AZO-Flav was tested to detect hypoxic and normoxic environments in cancer cells (HepG2). Compared to the normal condition, the fluorescence intensity in hypoxic conditions increased about 10-fold after 15 min. Prolonged incubation showed a 26-fold higher fluorescent intensity after 60 min. In addition, the fluorescence signal under hypoxia can be suppressed by an electron transport process inhibitor, diphenyliodonium chloride (DPIC), suggesting that reductases take part in the azo group reduction of AZO-Flav in a hypoxic environment. Therefore, this probe showed great potential application toward in vivo hypoxia detection.

2009 ◽  
Vol 37 (3) ◽  
pp. 631-640 ◽  
Author(s):  
D-D Ma ◽  
H-X Lu ◽  
L-S Xu ◽  
W Xiao

Paris polyphylla has been used to treat cancer in China for many years and components of the plant, such as polyphyllin D, may have potent antiproliferative effects in vitro To investigate the potential antitumour effects of polyphyllin D on cancer cells under hypoxia, Lewis lung cancer cells and mouse tracheal epithelial cells were cultured with or without polyphyllin D under normoxic and hypoxic conditions. Proliferation and apoptosis of cells were assayed. Real-time reverse transcription–polymerase chain reaction was used to quantify the expression of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) mRNA. Polyphyllin D decreased cell proliferation, increased apoptosis and inhibited expression of HIF-1α and VEGF mRNAs in Lewis cells. These effects were greater under hypoxic than normoxic conditions. Polyphyllin D did not show a cytotoxic effect in non-tumour cells (mouse skin fibroblasts and tracheal epithelial cells). These results suggest that polyphyllin D potentially has anticancer effects in vitro under hypoxia.


2011 ◽  
Vol 192 (3) ◽  
pp. 220-232 ◽  
Author(s):  
Vivian E. Fernand ◽  
Jack N. Losso ◽  
Robert E. Truax ◽  
Emily E. Villar ◽  
David K. Bwambok ◽  
...  

2017 ◽  
Vol 114 (6) ◽  
pp. E990-E998 ◽  
Author(s):  
Karin Hoppe-Seyler ◽  
Felicitas Bossler ◽  
Claudia Lohrey ◽  
Julia Bulkescher ◽  
Frank Rösl ◽  
...  

Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Liu ◽  
Huiqiong Huang ◽  
Xiaorong Qi ◽  
Ce Bian ◽  
Meng Cheng ◽  
...  

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.


2021 ◽  
Author(s):  
Viktor Maurer ◽  
Ajmal Zarinwall ◽  
Zunhao Wang ◽  
Stefan Wundrack ◽  
Nicole Wundrack ◽  
...  

Abstract BackgroundIn vitro and in vivo biosensing through surface-enhanced Raman scattering often suffer from signal contamination diminishing both the limit of detection and quantification. However, overcoming the lack of specificity requires excessive nanoparticle concentrations, which may lead to adverse side effects if applied to patients. ResultsWe propose encapsulation of iron oxide (FexOy) and gold (Au) nanoparticles (NPs) into the bilayer structure of transferrin-modified niosomes. This approach enables achieving greatly enhanced and contamination-free SERS-signals in vitro as well as a dual-targeting functionality towards MCF-7 breast cancer cells. An in-depth characterization of FexOyNPs- and AuNPs-loaded niosomes (AuNPs/FexOyNPs/NIO) after magnetic downstream processing reveals defined hybrid niosome structures, which show a long-term SERS-signal stability in various media such as MCF-7 cell culture medium. In vitro 2D-SERS imaging unveil a successful incorporation of a non-toxic dose of hybrid NPs into MCF-7 cells, which leads to strong and almost contamination-free SERS-signals. The measured signal-to-noise ratio of the in vitro signal exceeds the values required by DIN 32645 for the successful validation of a detection method. ConclusionsThe hybrid niosomes can be considered a promising and efficient agent for the establishment and commercialization of a highly sensitive detection kit for monitoring cancerous tissue.


2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  

Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.


2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Lisni Noraida Waruwu ◽  
Maria Bintang ◽  
Bambang Pontjo Priosoeryanto

Green tea (Camellia sinensis) is one of traditional plants that have the potential as an anticancer. The sample used in this research commercial green tea extract. The purpose of this study was to test the antiproliferation activity of green tea extract on breast cancer cell MCM-B2 in vitro. Green tea extract fractionated using three solvents, ie water, ethanol 70%, and n-hexane. Extract and fraction of green tea water have value Lethality Concentration 50 (LC50) more than 1000 ppm. The fraction of ethanol 70% and n-hexane had an LC50 value of 883.48 ppm and 600.56 ppm, respectively. The results of the phytochemical screening of green tea extract are flavonoids, tannins, and saponins, while the phytochemical screening results of n-hexane fraction are flavonoids and tannins. Antiproliferation activity was tested on breast cancer cells MCM-B2 and normal cells Vero by trypan blue staining method. The highest MCM-B2 cell inhibitory activity was achieved at a concentration of 13000 ppm green tea extract and 1000 ppm of n-hexane fraction, 59% and 59%, respectively. The extract and n-hexane fraction of green tea are not toxic to normal Vero cells characterized by not inhibiting normal cell proliferation. Keywords: antiproliferative, cancer cell MCM-B2, commercial green tea, cytotoxicity


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