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    A novel schiff base derivative for effective treatment of azoxymethane induced colon cancer
    (IJPSR, 2014) Doğan, Ayşegül; Başak, Neşe; Demirci, Selami; Telci, Dilek; Dede, Bülent; Tuzcu, Mehmet; Özercan, İbrahim Halil; Şahin, Kazım; Şahin, Fikrettin
    The field of cancer research has been emerged in recent years for the development of specific drugs to cancer treatment. New agents with the ability to provide efficient treatment by reducing side effects has led to new opportunities for improving agents for cytotoxic therapies. While there are several drugs for colon cancer treatment, researchers are trying to evaluate new agents or combinations of existing ones which can be used efficiently. Schiff bases with a wide range of variety and biological properties including anticancer activity might be used for colon cancer treatment. In the current study, a novel schiff base derivative synthesized by our group was tested in vivo for colon cancer. In a model of azoxymethane (AOM) induced colorectal cancer, chemopreventive properties of schiff base was also analyzed in rats. While AOM induced de novo crypt formation, adenocarcinoma and dysplasia development, schiff base application reduced the number of aberrant crypt foci (ACF), dysplasia or adenocarcinoma. Analysis of the intestinal mucosa showed that peritoneal administration of SB complex not only decreased the protein expression of COX-2, Bcl-2 and NF-κB but also enhanced the Bax expression suggesting the apoptotic and anti-proliferative effects for this compound. Our findings showed that SB complex might be used for the colorectal cancer treatment. Further studies are highly warranted to obtain additional insights and identify mode of action for the schiff base.
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    A NOVEL SCHIFF BASE DERIVATIVE FOR EFFECTIVE TREATMENT OF AZOXYMETHANE INDUCED COLON CANCER
    (Int Journal Pharmaceutical Sciences & Research, 2014) Dogan, Aysegul; Basak, Nese; Demirci, Selami; Telci, Dilek; Dede, Bulent; Tuzcu, Mehmet; Ozercan, Ibrahim Halil
    The field of cancer research has been emerged in recent years for the development of specific drugs to cancer treatment. New agents with the ability to provide efficient treatment by reducing side effects has led to new opportunities for improving agents for cytotoxic therapies. While there are several drugs for colon cancer treatment, researchers are trying to evaluate new agents or combinations of existing ones which can be used efficiently. Schiff bases with a wide range of variety and biological properties including anticancer activity might be used for colon cancer treatment. In the current study, a novel schiff base derivative synthesized by our group was tested in vivo for colon cancer. In a model of azoxymethane (AOM) induced colorectal cancer, chemopreventive properties of schiff base was also analyzed in rats. While AOM induced de novo crypt formation, adenocarcinoma and dysplasia development, schiff base application reduced the number of aberrant crypt foci (ACF), dysplasia or adenocarcinoma. Analysis of the intestinal mucosa showed that peritoneal administration of SB complex not only decreased the protein expression of COX-2, Bcl-2 and NF-kappa B but also enhanced the Bax expression suggesting the apoptotic and anti-proliferative effects for this compound. Our findings showed that SB complex might be used for the colorectal cancer treatment. Further studies are highly warranted to obtain additional insights and identify mode of action for the schiff base.
  • Küçük Resim Yok
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    Poloxamer P85 increases anticancer activity of Schiff base against prostate cancer in vitro and in vivo
    (Lippincott Williams & Wilkins, 2017) Demirci, Selami; Dogan, Aysegul; Turkmen, Nese Basak; Telci, Dilek; Caglayan, Ahmet B.; Beker, Mustafa C.; Kilic, Ertugrul
    Prostate cancer is the second most common cancer among men and the leading cause of death after lung cancer. Development of hormone-refractory disease is a crucial step for prostate cancer progression for which an effective treatment option is currently unavailable. Therefore, there is a need for new agents that can efficiently target cancer cells, decrease tumor growth, and thereby extend the survival of patients in late-stage castration-resistant prostate cancer. In the current study, a novel heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used to evaluate anticancer activity against prostate cancer in vitro and in vivo. Cell proliferation and cytotoxicity were evaluated by cell viability, gene, and protein expression assays in vitro. Results showed that the heterodinuclear copper(II)Mn(II) complex-P85 combination decreased cell proliferation by upregulating the apoptotic gene expressions and blocking the cell proliferation-related pathways. Tramp-C1-injected C57/B16 mice were used to mimic a prostate cancer model. Treatment combination of Schiff base complex and P85 significantly enhanced the cellular uptake of chemicals (by blocking the drug transporters and increased life time), suppressed tumor growth, and decreased tumor volume steadily over the course of the experiments. Overall, heterodinuclear copper(II) Mn(II) complex-P85 showed remarkable anticancer activity against prostate cancer in in vitro and in vivo. Anti-Cancer Drugs 28: 869-879 Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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    A Schiff base derivative for effective treatment of diethylnitrosamine induced liver cancer in vivo
    (Anticancer Drugs, 2015) Demirci, Selami; Doğan, Ayşegül; Başak, Neşe; Dede, Bülent; Telci, Dilek; Orhan, Cemal; Tuzcu, Mehmet; Şahin, Kazım; Şahin, Nurhan; Özercan, İbrahim; Şahin, Fikrettin
    Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.
  • Küçük Resim Yok
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    A Schiff base derivative for effective treatment of diethylnitrosamine-induced liver cancer in vivo
    (Lippincott Williams & Wilkins, 2015) Demirci, Selami; Dogan, Aysegul; Basak, Nese; Telci, Dilek; Dede, Bulent; Orhan, Cemal; Tuzcu, Mehmet
    Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II) Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-kappa B p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-kappa B (NF-kappa B p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
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    Schiff base poloxamer P85 combination prevents prostate cancer progression in C57 Bl6 mice
    (Prostate, 2016) Doğan, Ayşegül; Demirci, Selami; Başak, Neşe; Çağlayan, Ahmet Burak; Aydın, Safa; Telci, Dilek; Kılıç, Ertuğrul; Şahin, Kazım; Orhan, Cemal; Tuzcu, Mehmet; Şahin, Fikrettin; Doğan Ekinci, Işın Asiye
    BACKGROUND. Prostate cancer which is the second most common cause of death among men has a high incidence in recent years. Current therapeutic regimens should be improved to overcome drug resistance. At the metastatic stage, tumors become refractory to established chemotherapeutic treatments and cause serious problems at the clinics. Development of new drug molecules that are able to transport through the membrane easily and kill tumor cells rapidly is of great interest. METHOD. In the current study, a novel Heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used for prostate cancer treatment in vivo. Tramp-C1 cells injected animals were subjected to chemotherapeutic formulation treatment and results were analyzed by toxicology analysis, tumor volume measurements, and histopathological analysis. 0.5 mg/kg Schiff base was selected and combined with 0.05% P85 according to the toxicology analysis showing the enzyme levels, blood parameters, and multiple organ toxicity. RESULTS. Results demonstrated that Heterodinuclear copper(II)Mn(II) complex-P85 combination decreased tumor formation and tumor volume steadily over the course of experiments. CONCLUSIONS. Overall, Heterodinuclear copper(II)Mn(II) complex-P85 exerted remarkable anti-cancer activity in vivo in C57/B16 mice. Prostate 76:1454–1463, 2016. # 2016 Wiley Periodicals, Inc.
  • Küçük Resim Yok
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    Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Demirci, Selami; Dogan, Aysegul; Turkmen, Nese Basak; Telci, Dilek; Rizvanov, Albert A.; Sahin, Fikrettin
    Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II) Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the antiinflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. (C) 2016 Elsevier Masson SAS. All rights reserved.
  • Küçük Resim Yok
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    Schiff Base-Poloxamer P85 Combination Prevents Prostate Cancer Progression in C57/Bl6 Mice
    (Wiley, 2016) Dogan, Aysegul; Demirci, Selami; Turkmen, Nese Basak; Caglayan, Ahmet Burak; Aydin, Safa; Telci, Dilek; Kilic, Ertugrul
    BACKGROUNDProstate cancer which is the second most common cause of death among men has a high incidence in recent years. Current therapeutic regimens should be improved to overcome drug resistance. At the metastatic stage, tumors become refractory to established chemotherapeutic treatments and cause serious problems at the clinics. Development of new drug molecules that are able to transport through the membrane easily and kill tumor cells rapidly is of great interest. METHODIn the current study, a novel Heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used for prostate cancer treatment in vivo. Tramp-C1 cells injected animals were subjected to chemotherapeutic formulation treatment and results were analyzed by toxicology analysis, tumor volume measurements, and histopathological analysis. 0.5mg/kg Schiff base was selected and combined with 0.05% P85 according to the toxicology analysis showing the enzyme levels, blood parameters, and multiple organ toxicity. RESULTSResults demonstrated that Heterodinuclear copper(II)Mn(II) complex-P85 combination decreased tumor formation and tumor volume steadily over the course of experiments. CONCLUSIONSOverall, Heterodinuclear copper(II)Mn(II) complex-P85 exerted remarkable anti-cancer activity in vivo in C57/B16 mice. Prostate 76:1454-1463, 2016. (c) 2016 Wiley Periodicals, Inc.