Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens

Kazim Sahin,Engin Yenice,Mehmet Tuzcu,Cemal Orhan,Cengizhan Mizrak,Ibrahim H. Ozercan,Nurhan Sahin,Bahiddin Yilmaz,Birdal Bilir,Bulent Ozpolat,Omer Kucuk 대한암예방학회 2018 Journal of cancer prevention Vol.23 No.1

Background: Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene’s molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods: In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results: We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-B while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions: Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms. (J Cancer Prev 2018;23:25-36)

Zinc Picolinate in the Prevention of Leiomyoma in Japanese Quail

Nurhan Sahin,Mehmet Tuzcu,İbrahim Ozercan,Kazim Sahin,Ananda S. Prasad,Omer Kucuk 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

Epidemiologic studies suggest that zinc deficiency may be associated with increased risk of cancer. We investigated the effects of zinc picolinate supplementation on the development of leiomyomas, malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, and heat shock protein 70 (Hsp70) expression in Japanese quails. One hundred fifty quails (6 months old) were assigned to three treatment groups consisting of 50 birds in each group. Birds were fed either a basal diet or the basal diet supplemented with 30mg or 60mg of zinc/kg of diet. The animals were sacrificed after 350 days, and the tumors were identified. Zinc picolinate supplementation did not affect the number of leiomyomas compared to control birds (P>.05). However, the tumors in zinc-fed birds were smaller than those found in control birds (P=.01) Serum MDA, 8-isoprostane, and HAE levels were lower in the treatment groups than in the control group: MDA, 1.95 versus 0.93μmol/L; 8-isoprostane, 108 versus 85pg/mL; HAE, 1.55 versus 0.96μmol/L (P=.01 for all three parameters). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were 28.5, 23.6, and 20.1ng/mL, respectively (P=.01). Hsp70 expression was significantly decreased in zinc-treated birds (P<.01). The results indicate that dietary zinc picolinate supplementation reduces the growth of spontaneously occurring leiomyomas of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of zinc supplementation in the prevention and treatment of uterine leiomyoma in humans.

Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation

Shakir Ali,Amena Mahmood,Indusmita Routray,Tijjani Salihu Shinkafi,Kazim Sahin,Omer Kucuk 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.4

Background:Dried flower bud of Syzygium aromaticum (clove) is rich in eugenol, an antioxidant and antiinflammatory compound thatcan protect liver against injury. Clove, besides eugenol, also contains other pharmacologically active phytochemicals such as β-sitosteroland ascorbic acid. This study reports the effect of eugenol-rich fraction (ERF) of clove on liver cirrhosis induced by thioacetamide. Methods:Cirrhosis of the liver, which predisposes to hepatocellular carcinoma, was induced by administering thioacetamide (0.03%)in drinking water for 16 weeks. Cirrhotic animals were divided into two groups; the treated group was administered ERF for 9 weeks,one week after discontinuation of thioacetamide, while the other group received normal saline for a similar duration of time. Results:The treatment with ERF, as determined by histopathology and through a battery of biochemical markers of hepatic injury, oxidativestress and drug metabolizing enzymes, significantly ameliorated the signs of liver cirrhosis. It lowered the elevated levels ofalkalinephosphatase, γ-glutamyl transferase and other biochemical changes in liver cirrhosis. Histopathology of the liver corroborated the effectof ERF with biochemical findings. ERF treatment further inhibited cell proliferation, as demonstrated by reduced [3H]-thymidine uptake. Conclusions:Data provide evidence supporting the protective action of ERF on liver cirrhosis. The study assumes significance becausecirrhosis predisposes the liver to cancer, which is characterized by abnormal cell proliferation. ERF in this study is reportedto inhibithepatic cell proliferation and at the same time decrease oxidative stress, which might be the mechanism of protection against liver cirrhosis.

Cell Viability of Normal Human Skin Fibroblast and Fibroblasts Derived from Granulation Tissue: Effects of Nutraceuticals

Borawska, M.H.,Czechowska, S.K.,Markiewicz, R.,Hayirli, A.,Olszewska, E.,Kazim Sahin, D.V.M The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.2

The effects of lycopene, genistein, and epigallocatechin-3-gallate (EGCG) on cell viability were tested in vitro using a normal human skin fibroblast (NHSF) cell line (CRL-1474) and granulation tissue fibroblasts (GTFs) obtained from a patient with middle ear cholesteatoma. Cell cultures were added with lycopene (1, 5, and $10\;{\mu}M$), genistein (1, 5, 10, 25, and $50\;{\mu}M$), and EGCG (1, 5, 10, 25, and $50\;{\mu}M$) and their respective control cultures were established by adding 5 mL/L tetrahydrofuran (THF), 5 mL/L dimethyl sulfoxide (DMSO), and 5 mL/L DMSO. A colorimetric assay was employed for determining cell viability using thiazolyl blue tetrazolium bromide. Cell viability was expressed as a percentage of the control. Data were analyzed using two-way analysis of variance separately for each compound. Lycopene addition decreased viability of NHSFs and GTFs compared with THF addition (64.1%, 60.5%, and 100%, respectively, P < .0001). Genistein addition also increased viability of both NHSFs and GTFs compared with DMSO addition (P < .02). Increasing EGCG concentration tended to cause a linear increase in viability of NHSFs but did not alter viability of GTFs (P < .10). Our data suggest that genistein and EGCG but not lycopene could help maintaining or improving skin health through enhancing viability of skin fibroblasts.

The effects of coenzyme Q10 on oxidative stress and heat shock proteins in rats subjected to acute and chronic exercise

( Ragip Pala ),( Fahrettin Beyaz ),( Mehmet Tuzcu ),( Besir Er ),( Nurhan Sahin ),( Vedat Cinar ),( Kazim Sahin ) 한국운동영양학회 2018 Physical Activity and Nutrition (Phys Act Nutr) Vol.22 No.3

[Purpose] The aim of the study was to determine the effects of dietary CoQ10 on serum biochemical parameters, lipid peroxidation, and HSP expression in the liver and slow-twitch muscles (soleus and gastronemius deep portion) of exercise-trained rats. [Methods] A total of 42 Wistar albino rats were divided into six groups: 1) Control, 2) Coenzyme Q10 (CoQ10), 3) Chronic Exercise (CE), 4) CE + CoQ10, 5) Acute Exercise (AE), and 6) AE + CoQ10. The rats were subjected to the running test 5 days a week for 6 weeks after which CoQ10 was administered via the diet. AE (running on the treadmill until the rats were exhausted) was done on the last day. [Results] The results showed no significant difference in serum glucose and liver functions in any of the groups. However, CoQ10 and exercise treatment were found to lower cholesterol and triglyceride levels. Serum and muscle malondialdehyde (MDA) levels were found to be lower in the CE and CE + CoQ10 groups compared to the control group. The highest levels of HSP60, HSP70, and HSP90 in liver and muscle were found in the AE group, and the lowest levels were found in CE + CoQ10 group. CoQ10 supplementation reduced HSP expression in both CE- and AE-trained rats (P < 0.05). [Conclusion] The results showed that CoQ10 supplementation could reduce MDA levels, protect against oxidative damage, and regulate HSP expression in CE- and AE-trained rats. CE and CoQ10 were shown to reduce oxidative stress synergistically.