We report the application of a chemodosimeter 'turn on' fluorescent probe for detecting endogenous HS formation in cancer cells. Mito-HS showed a bathochromic shift in the UV-vis-absorption spectrum from 355 nm to 395 nm in the presence of HS. Furthermore, it showed an ∼43-fold fluorescence enhancement at λ = 450 nm in the presence of HS (200 μM). The cancer cell-specific fluorescence imaging reveals that Mito-HS has the ability to distinguish cancer cells from normal cells based on the level of endogenous HS formation. In due course, Mito-HS would be a powerful cancer biomarker based on its ability to estimate endogenous HS formation in living cells.
Endogenous H2S-stimulated protonophores released from MitoDP are a vanguard in creating mitochondria-targeted therapies for reducing mitochondrial activity in cancer cells.
Recent reports suggest that glucocorticoids (GCs), which can be synthesized in the oral mucosa, play an important role in cancer development. Therefore, the objectives of this study were to characterize the role of the oral GC system in oral cancer, and determine the effect of black raspberry (BRB) administration on GC modulation during oral cancer chemoprevention. We determined the expression of GC enzymes in various oral cancer cell lines, and investigated the role of the GC inactivating enzyme HSD11B2 on CAL27 oral cancer cells using siRNA mediated knockdown approaches. Using two in vivo models of oral carcinogenesis with 4-nitroquinoline-1-oxide (4NQO) carcinogen on C57Bl/6 mice and F344 rats, we determined the effect of BRB on GC modulation during HNSCC chemoprevention. Our results demonstrate that HSD11B2, which inactivates cortisol to cortisone, is downregulated during oral carcinogenesis in clinical and experimental models. Knockdown of HSD11B2 in oral cancer cells promotes cellular proliferation, invasion and expression of angiogenic biomarkers EGFR and VEGFA. An ethanol extract of BRB increased HSD11B2 expression on oral cancer cells. Dietary administration of 5% BRB increased Hsd11b2 gene and protein expression and reduced the active GC, corticosterone, in cancer-induced mouse tongues. Our results demonstrate that the oral GC system is modulated during oral carcinogenesis, and black raspberry administration upregulates Hsd11b2 during oral cancer chemoprevention. In conclusion, our findings challenge the use of synthetic glucocorticoids in head and neck cancer, and support the use of natural product alternatives that potentially modulate GC metabolism in a manner that supports oral cancer chemoprevention.
Diabetes is a metabolic disorder characterized by the presence of elevated glucose in the blood and enhanced oxidative stress. It affects the cellular homeostasis that leads to the development of micro‐and macro‐vascular complications. Monocytes are the primary immune cells present in the circulatory system. Under high‐glucose conditions, the cells undergo oxidative stress and secrete reactive oxygen species. The enhanced release of reactive species is known to modify biomolecules like proteins and nucleic acids. Protein carbonylation, one of the most harmful and irreversible protein modifications, is considered as a key player in the progression of diabetes and associated complications. Hence, the present study explores the identification of carbonylated proteins from the monocytes under diabetic stress and determination of their site of modification. Combined avidin affinity chromatography and bottom‐up proteomics experiments identified 13 consistently expressed carbonylated proteins. Most of the identified proteins were reported to have altered functions under diabetic conditions that contribute to the development of diabetes‐associated inflammation and complications. We were able to determine oxidative stress‐induced modifications on Lys, Val, Ile, Cys, Thr and Asp residues.
A water-soluble and biocompatible polymer, i.e. biotinylated poly(vinyl alcohol)-grafted graphene oxide (GO), was used as a nanocarrier for targeted delivery of anticancer drug camptothecin (CPT).
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