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Öğe Aldosterone induction alters micrornas profile in rat heart(WILEY-BLACKWELL, 2016) Karakurt, Serdar; Kagan, Esma Kubra[Abstract not Available]Öğe Alteration of enzyme activities and kinetic properties of GST and NQO1 with naturally occurring phenolic compounds(WALTER DE GRUYTER GMBH, 2015) Karakurt, Serdar; Sever, Melike; Celebioglu, Hasan Ufuk; Adali, OrhanObjective: Glutathione S-transferase (GST) and NAD(P)H:quinine oxidoreductase 1 (NQO1) are the enzymes important in cytoprotection and bioactivation of chemicals. This study has addressed effects of polyphenolic compounds; ellagic acid, quercetin, naringenin, resveratrol, rutin and hesperidin on rabbit liver GST and NQO1 enzyme activities. Methods: Cytosolic fractions were obtained from homogenized liver tissues of rabbit by differential centrifugation. After calculating IC50 values of individual enzymes for phenolic compounds, both Lineweaver-Burk and Dixon plots were drawn to determine the effect of phenolics on enzyme activity. Michaelis-Menten constant (K-m), maximum velocity (V-max), and inhibition constant (K-i) were calculated from Lineweaver-Burk and Dixon plots, respectively. Results: Resveratrol was found to be the most potent inhibitor for rabbit hepatic cytosolic GST activity with 75.9 +/- 2.06 mu M IC50 value while naringenin was the least potent one with IC50 value of 260 +/- 1.92 mu M. Hesperidin and quercetin were found to be the most and least potent inhibitors for NQO1 enzyme activity with IC50 values of 2.7 +/- 0.85 mu M and 13.8 +/- 0.91 mu M, respectively. Resveratrol and naringenin inhibited GST activity noncompetitively and mixed type with K-i of 6.2 mu M and 245 mu M, respectively; while both hesperidin with 0.64 mu M K-i value and quercetin with 3.5 mu M K-i value inhibited NQO1 activity in a competitive manner. Conclusion: These results indicate that phenolic compounds may modulate Phase II enzyme, GST and NQO1. Moreover, they can influence the metabolic activation of xenobiotic and toxic compounds metabolized by this enzyme.Öğe Alteration of enzyme activities and kinetic properties of GST and NQO1 with naturallyoccurring phenolic compounds(2015) Karakurt, Serdar; Sever, Melike; Celebioglu, Hasan Ufuk; Adali, OrhanAmaç: Glutatyon S-transferaz (GST) ve NAD(P)H:Kuinon Oksidoreduktaz 1 (NQO1) enzimleri kimyasal moleküllerin biyoaktivasyonunda rol alırken diğer yandan da onların zararlı etkilerine karşı koruma görevi görürler. Bu çalışma ile polifenolik bileşiklerden elajik asit, kuarsetin, naringenin, resveratrol, rutin ve hesperidinin tavşan karaciğer GST ve NQO1 enzim aktiviteleri üzerine etkileri amaçlanmıştır.Metod: Homojenize tavsan karaciğer dokusundan, diferansiyel santrifügasyon ile sitozolik fraksiyonlar elde edilmiştir. Her bir enzime ait fenolik bileşikler için IC50 değerleri hesaplandıktan sonra, fenoliklerin enzim aktiviteleri üzerine etkisini belirlemek icin Lineweaver-Burk ve Dixon grafikleri çizilmiştir. Bu grafiklerden Michaelis-Menten sabiti (Km), maksimum hız (Vmax) ve inhibisyon sabiti (Ki) hesaplanmıştır.Bulgular: Resveratrol, 75.92.06 ?M IC50 değeri ile tavsan karaciğer sitozolik GST aktivitesi için en güçlü inhibitor iken, naringenin 2601.92 ?M IC50 değeri ile en az güçlü inhibitor bulunmuştur. Hesperidin ve quersetin ise NQO1 enzimi için sırasıyla 2.70.85 ?M IC50 değeri ile en fazla ve 13.80.91 ?M IC50 değeri ile en düşük inhibitorler olarak bulunmuştur. Resveratrol ve naringenin GST aktivitesini sırasıyla 6.2 ?M Ki değeriyle yarışmasız ve 245 ?M Ki değeriyle karışık inhibisyon seklinde inhibe etmiştir. Öte yandan 0.64 ?M Kideğeri ile hesperidin ve 3.5 ?M Ki değeri ile quersetin NQO1 enzimini yarışmalı inhibisyon seklinde inhibe etmiştir.Sonuç: Bu bulgular göstermektedir ki fenolik bileşiklerin Faz II enzimlerinden GST ve NQO1'i modüle edebilir. Ayrıca, bu bileşikler bu enzimlerin metabolize ettiği ksenobiyotik ve toksik bileşiklerin metabolik aktivasyonunu etkileyebilir.Öğe Calixarenes in Lipase Biocatalysis and Cancer Therapy(BENTHAM SCIENCE PUBL LTD, 2016) Karakurt, Serdar; Kellici, Tahsin F.; Mavromoustakos, Thomas; Tzakos, Andreas G.; Yilmaz, MustafaCalixarenes are supramolecular structures characterized by their "calix" shape and their easy synthetic accessibility. They are amphiphilic in nature, thus they can bear in their structure both hydrophobic and hydrophilic features as well as charged groups. They are characterized by architectural plasticity responsible for their unique fine-tuned properties that can be shaped for an array of applications. Herein, we will focus, on their diverse available applications, and give special emphasis on biocatalysis and cancer therapy as two modern directions and emerging fields of interest that have been sporadically explored in the literature and can pave the way for the discovery of novel therapeutics. This review provides the first exhaustive examination on the enhanced catalytic activity and selectivity of calixarene-based encapsulated biocatalysts towards the synthesis of bioactive molecules. The application of functionalized calixarenes in cancer therapy is also analyzed towards the spatiotemporal control they can offer in targeted drug delivery.Öğe Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2016) Karakurt, Serdar; Semiz, Asli; Celik, Gurbet; Gencler-Ozkan, Ayse Mine; Sen, Alaattin; Adali, OrhanIn the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms, and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001).Öğe Dual-channel fluorescent probe based on bisphenol A-rhodamine for Zn2+ and Hg2+ through different signaling mechanisms and its bioimaging studies(ELSEVIER SCIENCE SA, 2017) Erdemir, Serkan; Yuksekogul, Mesut; Karakurt, Serdar; Kocyigit, OzcanA novel dual channel probe based on bisphenol A-rhodamine (BAR) was successfully designed and synthesized with high selectivity and sensitivity to Zn2+ and Hg2+ ions. BAR exhibited an effectively selective and sensitive recognition toward Zn2+ and Hg2+ ions through two different mechanisms (i.e. ESIPT and FRET) in pure MeCN and MeCN-H2O (v/v = 8/2, 5 mM, HEPES, pH 7.0) over other cations. The complexation properties of BAR with Zn2+ and Hg2+ ions were examined by H-1 NMR, C-13 NMR and FTIR experiments. The detection limits for Zn2+ and Hg2+ were 2.21 and 2.16 mu M, respectively. Furthermore, possible utilization of BAR as bio-imaging fluorescent probe to detect Hg2+ in human prostate cancer cell lines was ;also observed by Fluorescent Cell Imager. (C) 2016 Elsevier B.V. All rights reserved.Öğe The Effect of Hypothyroidism on XBP-1 Protein Expression Levels in Hippocampus and Amygdala in Rats(WILEY, 2017) Kandir, Sinan; Keskin, Ercan; Karakurt, Serdar[Abstract not Available]Öğe Formation of the inclusion complex of water soluble fluorescent calix[4]arene and naringenin: solubility, cytotoxic effect and molecular modeling studies(Taylor and Francis Ltd., 2019) Oğuz, Mehmet; Bhatti, Asıf Ali; Doğan, Berna; Karakurt, Serdar; Durdagı, Serdar; Yılmaz, MustafaNaringenin is considered as an important flavonoid in phytochemistry because of its important effect on cancer chemoprevention. Unfortunately its poor solubility has restricted its therapeutic applications. In this study, an efficient water-soluble fluorescent calix[4]arene (compound 5) was synthesized as host macromolecule to increase solubility and cytotoxicity in cancer cells of water-insoluble naringenin as well as to clarify localization of naringenin into the cells. Complex formed by host–guest interaction between compound 5 and naringenin was analyzed with UV–visible, fluorescence, FTIR spectroscopic techniques and molecular modeling studies. Stern–Volmer analysis showed binding constant value of Ksv 3.5 × 107 M?1 suggesting strong interaction between host and guest. Binding capacity shows 77% of naringenin was loaded on compound 5. Anticarcinogenic effects of naringenin complex were evaluated on human colorectal carcinoma cells (DLD-1) and it was found that 5-naringenin complex inhibits proliferation of DLD-1 cells 3.4-fold more compared to free naringenin. Fluorescence imaging studies show 5-naringenin complex was accumulated into the cytoplasm instead of the nucleus. Increased solubility and cytotoxicity of naringenin with fluorescent calix[4]arene makes it one of the potential candidates as a therapeutic enhancer. For deep understanding of host–guest interaction mechanisms, complementary multiscale molecular modeling studies were also carried out. Communicated by Ramaswamy H. Sarma. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.Öğe In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes(INST BIOLOSKA ISTRAZIVANJA SINISA STANKOVIC, 2017) Semiz, Asli; Celik-Turgut, Gurbet; Karakurt, Serdar; Akca, Hakan; Arslan, Sevki; Adali, Orhan; Sen, AlaattinIn the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mu M/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P) H: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels.Öğe Inhibitory action of Epilobium hirsutum extract and its constituent ellagic acid on drug-metabolizing enzymes(SPRINGER FRANCE, 2016) Celik, Gurbet; Semiz, Asli; Karakurt, Serdar; Gencler-Ozkan, Ayse Mine; Arslan, Sevki; Adali, Orhan; Sen, AlaattinEpilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxy-resorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content.Öğe MEASUREMENT UNCERTAINTY OF SPECTROPHOTOMETRIC DETERMINATION OF HEXAVALENT CHROMIUM IN WATER(POLYTECHNIC UNIV BUCHAREST, 2017) Karakurt, Sevtap; Karakurt, SerdarHexavalent chromium, + 6 oxidation state of chromium, is known to be human carcinogen besides damaging respiratory system, kidney, liver, skin and eyes and it can be discharged to surface waters through industrial processes such as welding on stainless steel, painting and electroplating. For the determination of this carcinogen hexavalent chromium in water, one of the most common analytical methods is the colorimetric diphenylcarbazide method. But, in order to report an analysis accurately, the measurement uncertainty of the parameter must be accompanied to the result of the analysis. The aim of this study is to present the measurement uncertainty of hexavalent chromium in water that is determined by the colorimetric method. The sources of uncertainty are specified by a cause-effect diagram and enlarged by using the calculations, thus giving the budget of uncertainty. At the end of the calculations, it was found that the measurement uncertainty was dominantly affected by the calibration curve whereas the precision had no significant effect on the measurement uncertainty. The expanded relative uncertainty was determined as +/- 0.05 with 95% confidence level.Öğe Modulatory effects of rutin on the expression of cytochrome P450s and antioxidant enzymes in human hepatoma cells(HRVATSKO FARMACEUTSKO DRUSTOV (HFD)-CROATION PHARMACEUTICAL SOC, 2016) Karakurt, SerdarExpression of a drug and xenobiotic metabolizing enzymes, cytochrome P450s (CYPs), and antioxidant enzymes can"be modulated by various factors. The flavonoid rutin was investigated for its anti-carcinogen and protective effects as well as modulatory action on CYPs and phase II enzymes in human hepatocellular carcinoma cel ls. Rutin inhibited proliferation of HEPG2 cells in a dose-dependent manner with the IC50 value of 52.7 mu mol L-1 and invasion of HEPG2 cells (21.6 %, p = 0.0018) and colony formation of those invaded cells (57.4 %, p < 0.0001). Rutin treatment also significantly increased early/late-stage apoptosis in HEPG2 cells (28.9 %, p < 0.001). Treatment by rutin significantly inhibited protein expressions of cytochrome P450-dependent CYP3A4 (75.3 %, p < 0.0001), elevated CYP1A1 enzymes (1.7-fold, p = 0.0084) and increased protein expressions of antioxidant and phase II reaction catalyzing enzymes, NQO1 (2.42-fold, p < 0.0001) and GSTP1 (2.03-fold, p < 0.0001). Besides, rutin treatment significantly inhibited mRNA expression of CYP3A4 (73.2 %, p=0.0014). Also, CYP1A1, NQO1 and GSTP1 mRNA expressions were significantly increased 2.77-fold (p = 0.029), 4.85 fold (p = 0.0051) and 9.84-fold (p < 0.0001), respectively.Öğe A new perylene bisimide-armed calix[4]-aza-crown as "turn on" fluorescent sensor for Hg2+ ion and its application to living cells(ELSEVIER SCIENCE SA, 2015) Erdemir, Serkan; Kocyigit, Ozcan; Karakurt, SerdarWe report the design and synthesis of a new perylene bisimide derivative containing calix[4]arene units (PB-CX[4]) as "turn on" fluorescent sensor for Hg2+ ion determination. PB-CX[4] showed highly selective and sensitive "turn-on" fluorescent responses toward Hg2+ ion based on photoinduced electron transfer (PET) mechanism in DMF/H2O (v/v, 9515). The binding analysis using a Job plot suggested that PB-CX[4] formed a 1:2 complex with He. The association constant (K) of PB-CX[4]-Hg2+ complex was found to be 1.66 x 10(9) M-7, with a detection limit of 5.56 x 10(-7) M. In addition, possible utilization of PB-CX[4] as bio-imaging fluorescent probe to detect Hg2+ in human colon cancer cell lines was also observed by confocal fluorescence microscopy. (C) 2015 Elsevier B.V. All rights reserved.Öğe New water soluble Hg2+ selective fluorescent calix[4]arenes: Synthesis and application in living cells imaging(PERGAMON-ELSEVIER SCIENCE LTD, 2017) Oguz, Mehmet; Bhatti, Asif Ali; Karakurt, Serdar; Aktas, Mehmet; Yilmaz, MustafaThe present study demonstrates the synthesis of water-soluble fluorescent calix[4]arenes (6 and 7) and its application in living cell imaging for Hg2+ detection at a low level. The synthesized fluorescent ligands 6 and 7 were characterized by H-1 NMR technique. The fluorescent study showed both water soluble ligands were Hg2+ selective and follow photo-induced electron transfer (PET) process. From the fluorimeter titration experiment detection limit was calculated as 1.14 x 10(-5) and 3.42 x 10(-5) for ligand 6 and 7, respectively. From the Benesi-Hildebrand plot binding constant values were evaluated as 666.7 and 733.3 M-1 for 6 and 7, respectively. The interactions between ligands 6 and 7 and Hg2+ were also demonstrated in living cells, SW-620, using Fluorescent Cell Imager. While ligands 6 and 7 alone show fluorescent properties, they loss their action with the presence of Hg2+ in SW-620 cells. (C) 2016 Elsevier B.V. All rights reserved.Öğe Synthesis and evaluation of fluorescence properties of Cu2+ selective azocalix[4]arenes and their application in living cell imaging(ELSEVIER SCIENCE SA, 2016) Elcin, Serkan; Deligoz, Hasalettin; Bhatti, Asif Ali; Oguz, Mehmet; Karakurt, Serdar; Yilmaz, MustafaThe present article deals with the detailed complexation study along with exploration of possible utilization of 25,26,27,28-tetra-hydroxy-11,23-di-(tert-butyl)-5,17-di-(2-antracenyl)azocalix[4]arene(7) and 25,26,27,28-tetra-hydroxy-11,23-di-(tert-butyl)-5,17-di-(1-pyreneyl)azocalix[4]arene (8) as bio-imaging fluorescent probe to detect Cu2+ in human colon cell line, SW-620, observed by fluorescence microscopy. Complexation properties of ligands 7 and 8 toward selected transition metal ions have been investigated by UV-vis and fluorescence spectroscopies. It has been noticed that ligands 7 and 8 are not only proved to be an efficient Cu2+ selective chromoionophore but also possess effective fluorescence properties by complexing with Cu2+ ions. The FTIR spectroscopic method has also been applied for further confirmation of the complexation phenomenon of ligands 7 and 8 with metal ion and were found to be adequate. Moreover, fluorescence microscopy studies showed that ligand 7 may be used as fluorescent probe to detect Cu2+ in living cells. (C) 2016 Elsevier B.V. All rights reserved.Öğe Synthesis of asymmetrical tridendate Schiff bases and metal complexes and investigation of anticarcinogen effects on human colon and cervical cancers(TAYLOR & FRANCIS INC, 2017) Sahin, Mustafa; Korkmaz, Hatice; Kocak, Nuriye; Sahin, Ozlem; Karakurt, Serdar; Yilmaz, MustafaThe metal complexes of Zn(II), Ni(II), Cu(II) and Pb(II) with asymmetrical Schiff bases were synthesized. The asymmetrical Schiff base was obtained through the condensation of 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde and biphenyl-4-carbaldehyde. The new Schiff base ligands (L-1' and L-2') and their metal complexes were characterized by TG/DTG, FT-IR, H-1-NMR, UV-Vis, ESR, powder XRD, elemental analysis, magnetic moment and fluorescence studies. The powder XRD studies indicate that Co(II) and Cu(II) complexes are amorphous, while Ni(II) and Zn(II) complexes are crystalline. The anticarcinogenic effects of L-1' and L-2' were also investigated against colon (SW-620) and cervical cancer (HeLa) cell lines and compound L-2' was found to possess the highest anticarcinogenic potential, with 16.7 mu M and 27.5 mu M of IC50 values for HeLa and SW620 cells, respectively.Öğe Synthesis of benzimidazole Schiff base derivatives and cytotoxic effects on colon and cervix cancer cell lines(BIOINTERFACE RESEARCH APPLIED CHEMISTRY, 2017) Arslaner, Cennet; Karakurt, Serdar; Koc, Ziya ErdemDuring the last few years the potential of benzimidazole derivatives in agrochemical and medicinal properties have been subjected to investigation. benzimidazole derivatives have been received central attention due to their significant antimicrobial, antibacterial, antifungal, anti-HIV, anticancer, and a wide array of other biological activities. The formation of 2-aryl-substituted benzimidazoles, by the polyphosphoric acid-catalyzed condensation of a carboxylic acid, with an o-amino-arylamine is described. The condensations proceed in good yield to give products which, in certain instances, are not readily attainable by conventional condensation techniques. The study of Benzimidazole containing Schiff bases is also of interest as some of them have shown the ability to anticancer. The structures of the compounds were identified by FT-IR, H-1 NMR, C-13 NMR and elemental analysis. Cytotoxic effects of benzimidazole derivatives on human cervical and colon cancer cell lines HeLa and SW-620 was determined spectrophotometrically by using Alamar Blue. Benzimidazole derivatives selectively inhibited proliferation of cancerous cell lines. None of the benzimidazole Schiff base derivatives inhibits proliferation of SW-620 while 4-APbzlH, 4SAPbz1H and 3SAPbz1H dose dependently inhibit proliferation of HeLa cells with IC50 of 230 mu M, 110.6 mu M and 101.3 mu M, respectively.Öğe Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes(BENTHAM SCIENCE PUBL LTD, 2016) Karakurt, Serdar; Adali, OrhanThe aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 mu M and 29.1 mu M, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa.