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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-κB and TGF-α pathways. Down-regulatory (CDKN1B, AKT1, IFN-γ) 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. [ABSTRACT FROM AUTHOR]

Summary: Background: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen‐activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP‐1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. Objectives: In this study, we investigated the effects of melatonin on UVA‐irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time‐dependent manner which have not been clearly elucidated yet. Methods: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub‐cytotoxic dosage (20 J/cm2) after pretreatment with melatonin (1 μmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. Results: Our results clearly show that melatonin decreases UVA‐induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP‐1 signal transduction pathway and production of matrix metalloproteinases in a time‐dependent manner. Conclusion: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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Acute myeloid leukemia (AML) is a severe blood cancer with less than 50 % long-term survival. Despite advancements in treatment options, relapse is still the major obstacle. The main reason of this problem is ineffective targeting of leukemic stem cells (LSCs), which play an important role in tumor development and relapse. In our previous studies, we found that casticin, the major polyphenolic component of Vitex trifolia’s fruit, targets both leukemic cells and LSCs without affecting healthy tissues. Therefore, in this study, we aimed to investigate the effect of casticin-mediated cell death in relation to the LSCs-favored survival pathways at gene and protein expression levels using in vitro LSC-like and parental leukemic cell models.We validated the LSC character of KG1a and KG1 cells (84.55 % CD34+, CD38- and 93.55 % CD34+, CD38+, respectively) by flow cytometry. For the investigation of casticin’s mechanism of action, we employed real time-PCR, western blotting and bioinformatics analyses.Our results showed an increase in cleaved PARP/β-actin ratio but no change in LC3BI/II and SQSTM/β-actin ratios. Our gene expression, bioinformatics and immunoblotting analyses represented significant decrease in Shh, Gli and Wnt levels. We also elucidated a possible crosstalk between Hedgehog and other oncogenic cascades via the Gli, Notch, YAP, p38, Mcl-1, and Myc proteins in casticin mediated anti-leukemic effect.In conclusion, we found that casticin induces apoptosis in both LSC-like and parental leukemia cells mainly by suppressing Shh signaling, which is crucial for LSC survival and AML relapse. [ABSTRACT FROM AUTHOR]

Recently, tendency in uptake of protein supplements with daily diet have been increasing. The most preferred protein supplements are casein, whey or soya protein. Whey protein, particularly, is preferred due to its high caloric value and its ability to increase body muscle mass. Although, some researches mention the benefits of Whey protein, it is argued that it may cause organ damage in short/long-term usage. Any experimental study about effects of short/long-term usage of Whey has not existed yet. The aim in this study, with the constructed experimental model, is monitoring possible liver damage in short and long-term. With this aim any change in values of Tumor necrosis factor a(TNFα), Interleukin-1β (1L-1β), Interleukin-6 (IL6) which are liver tissue molecular mediators and CK18-M30 which may increase due to apoptotic cell damage were analyzed. In this work, the model of short/long term food intake in humans was applied according to the experimental model of Quinn R. for the studies with rats. Three groups composed of 10 individuals of 30 male Wistar rats were used in the study [C: Control group (n=10), WS: those who was fed with whey protein for the short- term (n=10), WL: those who was fed with whey protein for the long-term (n=10)]. When the data is compared with control group, any significant difference in the levels of TNFα, IL-6, IL-1β, has not been determined in WS group (p >0.05). In the WL group, a significant increase has been determined (p <0.05). Also, if the data of serum CK-18 were analyzed, while in WS group any significant difference was not determined (p >0.05), in WL group a significant increase was determined (p <0.05). Consequently, our study shows long-term Whey protein intake causes increase of molecular mediators in liver tissue and the damage will be determined with the serum indicator CK-18. Based on our study, we suggest the ones exercising should not take Whey protein for long-terms such as 2 years. [ABSTRACT FROM AUTHOR]

Günümüzde özellikle kas kitlesini arttırmaya yönelik spor çalışmalarında günlük diyete ek olarak protein desteklerine yönelim artmıştır. Kazein, Whey veya soya proteini en çok tercih edilen protein destekleridir. Özellikle Whey proteini yüksek kalorik değeri ve kas kitlesini arttırması nedeniyle sık tercih edilmektedir. Yapılan çalışmalar çoğunlukla Whey proteinin sağladığı yararları belirtse de kısa veya uzun dönem kullanımda organlara verebileceği zararlar halen tartışma konusudur. Whey proteinin kısa/uzun dönem kullanımındaki etkilerine yönelik deneysel bir çalışma ise henüz bulunmamaktadır. Bu çalışmada amaç; oluşturulan deneysel modelde kısa ve uzun dönemde olası karaciğer hasarının incelenmesidir. Bu amaçla karaciğer dokusu moleküler mediatörleri olan Tümör nekroz faktör a (TNFa), İnterlökin-1 b (1L- 1b), İnterlökin-6 (IL-6) ve apoptotik hücre hasarında artış gösterebilen bir serum belirteci olan CK18-M30'un değişimi izlenmiştir. Bu çalışma, insanlarda kısa/uzun dönem besin alımını yansıtan, Quinn R.'nın rat çalışmaları için önerilen deneysel model ile gerçekleştirilmiştir. Çalışmaya 30 erkek sıçan katılarak 3 gruba ayrılmıştır [K: Kontrol grubu (n=10), WK: Kısa dönem whey proteini ile beslenen (n=10), WU: Uzun dönem dönem whey proteini ile beslenen (n=10)]. Veriler kontrol grubu ile karşılaştırıldığında WK grubunda TNFa, IL-6, IL- 1b düzeylerinde anlamlı bir fark saptanmadı (p >0.05), WU grubunda ise kontrol grubuna göre anlamlı derecede fark saptandı (p <0.05). Aynı gruplarda yapılan serum CK18 verileri değerlendirildiğinde WK grubunda anlamlı fark saptanmazken (p >0.05), WU grubunda anlamlı düzeyde artış saptandı(p0.05). Sonuç olarak çalışmamız; uzun dönem Whey protein alımının karaciğer dokusunda moleküler mediatörlerin artışına neden olan bir hasar oluşturduğunu ve bu hasarın serum belirteci olan CK18 ile belirlenebilir düzeyde olduğunu göstermektedir. Çalışmamıza dayanarak spor yapanların 2 yıl gibi uzun dönemlerde Whey protein alımı yapmamaları gerektiğini öngörmekteyiz. [ABSTRACT FROM AUTHOR]