Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate

© 2022 Elsevier B.V.The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms. In this study, we found that TPP caused cytotoxicity on human skin keratinocytes (HaCaT) and significantly inhibited the proliferation and cell migration in a concentration-dependent manner. Additionally, HaCaT cells were sensitive to TPP-induced apoptosis. Reactive oxygen species production was induced with TPP, which increased the protein carbonylation and lipid peroxidation levels. Moreover, TPP inhibited proteasome activity and increased the accumulation of ubiquitinated proteins. Exposure to TPP significantly increased the HSP90, HSP70, GRP94 and GRP78 protein levels. Overall, our findings indicate that TPP may pose a risk to human health and contribute to the current understanding of the risks of TPP at the molecular level

Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells

Chronic myeloid leukemia is a major hematopoietic malignancy characterized by expansion of myeloid cells. In this study, we have investigated whether quercetin, curcumin and their combination induce apoptosis and inhibit growth of K562 cells. We have observed that quercetin and curcumin combination induced apoptosis accompanied by increased ROS and decreased GSH levels as well as loss of mitochondrial membrane potential. Our mRNA and protein expression results suggested that cytochrome c was released from mitochondria causing PARP and caspase-9 cleavages, the hallmarks of mitochondrial apoptotic pathway. We believe that triggering of apoptosis is mostly via mitochondrial pathway and ROS generation may induce impairment of mitochondrial membrane potential. The use of quercetin and curcumin combination potentiates individual apoptotic effects of the polyphenols and reduces their effective dose thereby preventing potential toxic effects on normal cells. Additional preclinical studies and clinical trials are certainly required to further validate their usefulness as potent anticancer agents

Whey Protein Versus Whey Protein Hydrolyzate for the Protection of Azoxymethane and Dextran Sodium Sulfate Induced Colonic Tumors in Rats

Recent studies have shown that whey protein has many useful effects including its anti-cancer effect. In this study we have compared the protective effect of dietary whey protein with whey protein hydrolyzate against azoxymethane and dextran sodium sulfate induced colon cancer in rats. We used a rat model of the colon cancer induced by administration of azoxymethane followed by repeated dextran sodium sulfate ingestion which causes multiple tumor development. Colon tissues were analyzed histologically in addition to biochemical analyses performed by measuring lipid peroxidation, protein oxidation and glutathione levels in both of colon and liver tissues of rats after sacrification. Macroscopic and microscopic tumors were identified in all groups that received azoxymethane followed by repeated dextran sodium sulfate. Group fed with whey protein hydrolyzate showed significantly less macroscopic and microscopic tumor development compared with group fed with whey protein. The protocol applied to generate an appropriate model of colon cancer was successful. Whey protein hydrolyzate was found to be more effective in preventing colon tumor development compared with whey protein

Anti-cancer effects of curcumin, quercetin and tea catechins

Polyphenols are present in high amounts in all parts of plants including roots, seeds, flowers, leaves, branches and trunk as well as plant derived products such as tea, coffee and wine. Extensive amount of information is available on biological effects of polyphenols including antioxidant, anti-cancer, anti-inflammatory, anti-coagulant and anti-microbial activities. In recent years, researchers have turned their interest towards identifying molecular mechanisms underlying the anti-cancer effects of these compounds. However, the limited bioavailability of polyphenols and the existence of differences in cancer cells in terms of intracellular mechanisms affected has necessitated the use of specific approaches to individual cancer cell types as well as methods of increasing bioavailability. In this review, the structures, bioavailability, biological activities and molecular mechanisms of anti-cancer effects of curcumin, quercetin and tea catechins are discussed

Effect of ketone bodies on viability of human breast cancer cells (MCF-7)

Objective: Cancer cells exhibit an elevated glycolytic phenotype under aerobic conditions, which is known as the Warburg effect. Recent studies have also shown that cancer cells are glucose-dependent and cannot use ketone bodies as a primary source of energy. In this study, we have investigated the effects of ketone bodies on viability of breast cancer cells considering that breast cancer cells would not use ketone bodies as a primary energy source. Materials and Methods: In this study we have used MCF-7 cells, which are breast cancer cells that cannot use ketone bodies as a primary energy source and human foreskin fibroblast cells (HFF) as controls. We measured cell viability in both cells cultured in the presence or absence of glucose as well as the ketone bodies acetoacetate and beta-hydroxybutyrate. Results: Cell viability was significantly decreased in response to ketone bodies compared with control media in MCF-7 cells whereas in control cells (HFF) cell viability was not changed. Conclusion: In light of the data obtained, we suggest that dietary manipulation with the use of ketone bodies may be a new therapeutic strategy for breast cancer

Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells: II. Signal Transduction Pathways Involved

Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties. They were successfully used against different human cancers, especially chronic myeloid leukemia cancer cells. We have previously investigated anti-proliferative and apoptotic effects of quercetin and curcumin combination in K562 cells. Our data showed that they had beneficial synergistic effects. Based on these findings, we aimed to clarify signaling pathways involved in synergistic combination treatment with quercetin and curcumin in these cells. Proteins were investigated by Western blotting and by confocal microscopy. Changes in several genes in 10 different pathways related to cell proliferation, apoptosis, cell cycle, inflammation, hypoxia and oxidative stress were observed. Combination of quercetin and curcumin was effective on genes that were particularly related to p53, NF-kappa B and TGF-alpha pathways. Down-regulatory (CDKN1B, AKT1, IFN-gamma) and up-regulatory (BTG2, CDKN1A, FAS) effects on genes and related protein expressions may provide a multi-targeted therapy potential for chronic myeloid leukemia cancer cells without affecting healthy cells