ABSTRACT
[This retracts the article DOI: 10.3892/ol.2018.9173.].
ABSTRACT
Many natural products could induce apoptosis through mitochondrial pathways. However, direct interactions between natural products and mitochondria have rarely been reported. In this work, the effects and regulatory mechanisms of Jaceosidin on the isolated rat liver mitochondria have been studied. The results of the experiments which by introducing exogenous Ca2+ illustrated that Jaceosidin has the protective effects on the structure and function of the isolated mitochondria. These protective effects were related to the chelation of Ca2+ with Jaceosidin. Besides, Jaceosidin could scavenge reactive oxygen species produced during electron transport, and weaken the mitochondrial lipid peroxidation rate, which may be attributed to the antioxidant effect of phenolic hydroxyl groups of Jaceosidin. In addition, Jaceosidin has some damage effects on mitochondrial function, such as the inhibition of mitochondrial respiration and the increase of mitochondrial membrane fluidity. These results of this work provided comprehensive information to clarify the mechanisms of Jaceosidin on mitochondria, which may be the bidirectional regulatory mechanisms.
Subject(s)
Flavonoids/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Adenosine Triphosphate/metabolism , Animals , Calcium/metabolism , Electron Transport/drug effects , Flavonoids/chemistry , Hydrogen/metabolism , Lipid Peroxidation , Membrane Fluidity , Membrane Potential, Mitochondrial/drug effects , Mitochondria/ultrastructure , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Mitochondrial Membranes/drug effects , Mitochondrial Membranes/metabolism , Molecular Structure , Permeability/drug effects , Potassium/metabolism , Rats , Reactive Oxygen Species/metabolismABSTRACT
Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.
Subject(s)
Arsenicals/pharmacology , Disease Progression , Lactate Dehydrogenase 5/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Organic Chemicals/pharmacology , Animals , Arsenicals/chemical synthesis , Arsenicals/chemistry , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Respiration/drug effects , Female , Glutathione/metabolism , Humans , Ki-67 Antigen/metabolism , Lactate Dehydrogenase 5/antagonists & inhibitors , Mice, Nude , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/ultrastructure , Organic Chemicals/chemical synthesis , Organic Chemicals/chemistry , Oxygen Consumption/drug effects , Pyruvate Dehydrogenase Complex/metabolism , Rats, Wistar , Reactive Oxygen Species/metabolism , Thioredoxins/metabolism , Xenograft Model Antitumor AssaysABSTRACT
The present study was planned to investigate miR-143 expression during stomach cancer. The study explored the relationship between miR-143 expression and clinicopathological characteristics including proliferation, migration and apoptosis of stomach cancer cells. Sixty-three samples from each of stomach cancer tissue and surrounding tissue were obtained. Total RNA was extracted. The expression levels of miR-143 from stomach cancer tissue as well as from surrounding tissue were measured by semi-quantitative PCR. The effects of miR-143 overexpression on the migration of stomach cancer cells were examined by Transwell assay. The effects of miR-143 overexpression on the apoptosis of stomach cancer cells were examined by flow cytometer. The expression level of miR-143 was significantly decreased in stomach cancer tissues in comparison to surrounding tissues (P<0.01). Moreover, the expression of miR-143 related well with the tumor size, TNM stage, lymphatic metastasis and relapse (P<0.01). On the other hand, stomach cancer cell line with overexpression of miR-143, showed significant decline in proliferation rate and migration rate comparison to control cells (P<0.01). However, it showed significant higher in apoptosis rate (P<0.01). The present study concluded that expression of miR-143 is low during stomach cancer. Further, higher expression levels of miR-143 have the ability to decline proliferation and migration of stomach cancer cells. In this manner, the expression level of miR-143 could be used as an important factor to determine the severity of stomach cancer.
ABSTRACT
In this work, the effects of two non-ionic, non-hydroxyl organic solvents, dimethyl sulfoxide (DMSO) and dimethyl formamide (DMF) on the morphology and function of isolated rat hepatic mitochondria were investigated and compared. Mitochondrial ultrastructures impaired by DMSO and DMF were clearly observed by transmission electron microscopy. Spectroscopic and polarographic results demonstrated that organic solvents induced mitochondrial swelling, enhanced the permeation to H+/K+, collapsed the potential inner mitochondrial membrane (IMM), and increased the IMM fluidity. Moreover, with organic solvents addition, the outer mitochondrial membrane (OMM) was broken, accompanied with the release of Cytochrome c, which could activate cell apoptosis signaling pathway. The role of DMSO and DMF in enhancing permeation or transient water pore formation in the mitochondrial phospholipid bilayer might be the main reason for the mitochondrial morphology and function impaired. Mitochondrial dysfunctions induced by the two organic solvents were dose-dependent, but the extents varied. Ethanol (EtOH) showed the highest potential damage on the mitochondrial morphology and functions, followed by DMF and DMSO.
Subject(s)
Dimethyl Sulfoxide/toxicity , Dimethylformamide/toxicity , Mitochondria/ultrastructure , Animals , Cytochromes c/metabolism , Dose-Response Relationship, Drug , Ethanol/toxicity , Intracellular Membranes/metabolism , Mitochondrial Membranes/drug effects , Mitochondrial Swelling/drug effects , Permeability/drug effects , RatsABSTRACT
The purpose of this study was to quantify hepatitis B virus DNA by direct real-time PCR from serum without the need for DNA extraction. Crossing point (Cp) values were determined automatically using the second derivative maximum mode. Since serum samples from patients are inevitably haemolysed, lipaemic or icteric, the interference of endogenous substances from the serum in real-time PCR was evaluated. The result showed that, although serum protein quenched the intensity of fluorescence, the Cp value adopted to calculate the quantity of DNA copies remained unchanged. Importantly, real-time PCR from serum with or without DNA extraction reached a high level of concordance. This direct serum PCR method without the DNA extraction and gel electrophoresis allows for substantial labour and cost savings. In addition, it is also suitable for rapid DNA quantification during clinical diagnosis.
