Cyproheptadine

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Zahra Khazaeipour - One of the best experts on this subject based on the ideXlab platform.

  • Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz a randomized clinical trial
    Aids Patient Care and Stds, 2013
    Co-Authors: Fatemeh Dabaghzadeh, Padideh Ghaeli, Hossein Khalili, Abbas Alimadadi, Sirous Jafari, Shahin Akhondzadeh, Zahra Khazaeipour
    Abstract:

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a Cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

Chengda Hsu - One of the best experts on this subject based on the ideXlab platform.

  • Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting gsk3β to suppress mtor and β catenin signaling pathways
    Cancer Letters, 2016
    Co-Authors: Hsiao Yen Hsieh, Cheng Huang Shen, Ru Inn Lin, Yu Min Feng, Shih Yuan Huang, Yuan Hung Wang, Chengda Hsu, Michael W Y Chan
    Abstract:

    Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the therapeutic effect of Cyproheptadine in urothelial carcinoma (UC) has never been explored. In this study, we determined the effect of Cyproheptadine on the growth of five human UC cell lines and an in vivo xenograft model. The results showed that Cyproheptadine exerted an inhibitory effect on the proliferation of UC cells both in vitro and in vivo. Cyproheptadine also induced cell cycle arrest in the G1 phase, subsequently followed by apoptosis and necrosis. The underlying mechanisms of cell cycle arrest were associated with the reduction of c-Myc, induction of p21 and p27, and the stabilization of Rb expression. In addition, the suppression of the GSK3β/TSC2/mTOR pathway and deregulation of the GSK3β/β-catenin signaling were observed in Cyproheptadine-treated UC cells. Furthermore, Cyproheptadine-induced apoptosis was associated with ANGPTL4 expression followed by activation of caspase3 and PARP in UC cells. Our experimental results provide evidence that Cyproheptadine is a suitable therapeutic agent for the treatment of UC.

  • Cyproheptadine an antihistaminic drug inhibits proliferation of hepatocellular carcinoma cells by blocking cell cycle progression through the activation of p38 map kinase
    BMC Cancer, 2015
    Co-Authors: Yu Min Feng, Hsiao Yen Hsieh, Syueyi Chen, Chinwen Feng, Yuhsin Chen, Chengda Hsu
    Abstract:

    Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide. However, current chemotherapeutic drugs for HCC are either poorly effective or expensive, and treatment with these drugs has not led to satisfactory outcomes. In a 2012 case report, we described our breakthrough finding in two advanced HCC patients, of whom one achieved complete remission of liver tumors and the other a normalized α-fetoprotein level, along with complete remission of their lung metastases, after the concomitant use of thalidomide and Cyproheptadine. We assumed the key factor in our effective therapy to be Cyproheptadine. In this study, we investigated the antiproliferative effects and molecular mechanisms of Cyproheptadine. The effect of Cyproheptadine on cell proliferation was examined in human HCC cell lines HepG2 and Huh-7. Cell viability was assayed with Cell Counting Kit-8; cell cycle distribution was analyzed by flow cytometry. Mechanisms underlying Cyproheptadine-induced cell cycle arrest were probed by western blot analysis. Cyproheptadine had a potent inhibitory effect on the proliferation of HepG2 and Huh-7 cells but minimal toxicity in normal hepatocytes. Cyproheptadine induced cell cycle arrest in HepG2 cells in the G1 phase and in Huh-7 cells at the G1/S transition. The Cyproheptadine-induced G1 arrest in HepG2 cells was associated with an increased expression of HBP1 and p16, whereas the G1/S arrest in Huh-7 cells was associated with an increase in p21 and p27 expression and a dramatic decrease in the phosphorylation of the retinoblastoma protein. Additionally, Cyproheptadine elevated the percentage of Huh-7 cells in the sub-G1 population, increased annexin V staining for cell death, and raised the levels of PARP and its cleaved form, indicating induction of apoptosis. Finally, Cyproheptadine-mediated cell cycle arrest was dependent upon the activation of p38 MAP kinase in HepG2 cells and the activation of both p38 MAP kinase and CHK2 in Huh-7 cells. Our results demonstrate that a non-classical p38 MAP kinase function, regulation of cell cycle checkpoints, is one of the underlying mechanisms promoted by Cyproheptadine to suppress the proliferation of HCC cells. These results provide evidence for the drug’s potential as a treatment option for liver cancer.

  • abstract 4566a effect of the anti histaminic Cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms
    Cancer Research, 2014
    Co-Authors: Chengda Hsu, Yu Min Feng, Syueyi Chen, Jingwen Feng
    Abstract:

    Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide; however, current chemotherapeutic drugs for hepatocellular carcinoma (HCC) are either poorly effective or expensive. The majority of patients can9t have good outcomes by taking these drugs. Currently, we had a breakthrough finding in a case report of two patients with advanced HCC. We found one had complete remission of liver tumors, one had decrease of their alpha-fetoprotein levels and that both their lung metastasis had complete remission after the concomitant use of thalidomide and Cyproheptadine. In light of a previous study that Cyproheptadine affects the cell cycle and impedes leukemia cell growth by suppressing the action of transcription factor of cyclin D, we assume that Cyproheptadine is the key factor in this treatment. Therefore, the purpose of this study was to investigate whether Cyproheptadine inhibits HCC cell growth by impeding cancer cell cycle and to explore the molecular mechanisms of Cyproheptadine-induced cell cycle arrest. First, we confirmed that Cyproheptadine had inhibition effect on two HCC cell lines, HepG2 and Huh-7, by cell viability assay. Besides, to explore how Cyproheptadine affects HCC cell cycle we analyzed DNA content by flow cytometry and found cell cycle arrest at the G1 to S transition in HepG2 cells and at the S to G2 transition in Huh-7 cells. Finally, we investigated the mechanism of Cyproheptadine-induced cell cycle arrest using western blot analysis. Interestingly, our results showed that Cyproheptadine promoted P38 activation by phosphorylation than subsequently stabilized P16 and caucused hypophosphorylation of Rb in HepG2 cells. On the other hand, Cyproheptadine not only promoted P38 activation but also activated ATM/Chk2 pathway to stabilize P21 in Huh-7 cells. These novel results demonstrated that Cyproheptadine suppressed HCC cells through the Non-classical P38 MAP Kinase Functions: Cell Cycle Checkpoints and ATM/Chk2 pathway, and provided a potential treatment option in HCC. Citation Format: Cheng-Da Hsu, Yu-Min Feng, Syue-Yi Chen, Jing-Wen Feng. Effect of the anti-histaminic Cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4566A. doi:10.1158/1538-7445.AM2014-4566A

  • unexpected remission of hepatocellular carcinoma hcc with lung metastasis to the combination therapy of thalidomide and Cyproheptadine report of two cases and a preliminary hcc cell line study
    Case Reports, 2012
    Co-Authors: Yu Min Feng, Chinwen Feng, Solomon Chihcheng Chen, Chengda Hsu
    Abstract:

    We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and Cyproheptadine. The use of Cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that Cyproheptadine effectively reduced the viability of two HCC cell lines.

Fatemeh Dabaghzadeh - One of the best experts on this subject based on the ideXlab platform.

  • Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz a randomized clinical trial
    Aids Patient Care and Stds, 2013
    Co-Authors: Fatemeh Dabaghzadeh, Padideh Ghaeli, Hossein Khalili, Abbas Alimadadi, Sirous Jafari, Shahin Akhondzadeh, Zahra Khazaeipour
    Abstract:

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a Cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

Gang Cui - One of the best experts on this subject based on the ideXlab platform.

Yu Min Feng - One of the best experts on this subject based on the ideXlab platform.

  • Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting gsk3β to suppress mtor and β catenin signaling pathways
    Cancer Letters, 2016
    Co-Authors: Hsiao Yen Hsieh, Cheng Huang Shen, Ru Inn Lin, Yu Min Feng, Shih Yuan Huang, Yuan Hung Wang, Chengda Hsu, Michael W Y Chan
    Abstract:

    Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the therapeutic effect of Cyproheptadine in urothelial carcinoma (UC) has never been explored. In this study, we determined the effect of Cyproheptadine on the growth of five human UC cell lines and an in vivo xenograft model. The results showed that Cyproheptadine exerted an inhibitory effect on the proliferation of UC cells both in vitro and in vivo. Cyproheptadine also induced cell cycle arrest in the G1 phase, subsequently followed by apoptosis and necrosis. The underlying mechanisms of cell cycle arrest were associated with the reduction of c-Myc, induction of p21 and p27, and the stabilization of Rb expression. In addition, the suppression of the GSK3β/TSC2/mTOR pathway and deregulation of the GSK3β/β-catenin signaling were observed in Cyproheptadine-treated UC cells. Furthermore, Cyproheptadine-induced apoptosis was associated with ANGPTL4 expression followed by activation of caspase3 and PARP in UC cells. Our experimental results provide evidence that Cyproheptadine is a suitable therapeutic agent for the treatment of UC.

  • Cyproheptadine an antihistaminic drug inhibits proliferation of hepatocellular carcinoma cells by blocking cell cycle progression through the activation of p38 map kinase
    BMC Cancer, 2015
    Co-Authors: Yu Min Feng, Hsiao Yen Hsieh, Syueyi Chen, Chinwen Feng, Yuhsin Chen, Chengda Hsu
    Abstract:

    Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide. However, current chemotherapeutic drugs for HCC are either poorly effective or expensive, and treatment with these drugs has not led to satisfactory outcomes. In a 2012 case report, we described our breakthrough finding in two advanced HCC patients, of whom one achieved complete remission of liver tumors and the other a normalized α-fetoprotein level, along with complete remission of their lung metastases, after the concomitant use of thalidomide and Cyproheptadine. We assumed the key factor in our effective therapy to be Cyproheptadine. In this study, we investigated the antiproliferative effects and molecular mechanisms of Cyproheptadine. The effect of Cyproheptadine on cell proliferation was examined in human HCC cell lines HepG2 and Huh-7. Cell viability was assayed with Cell Counting Kit-8; cell cycle distribution was analyzed by flow cytometry. Mechanisms underlying Cyproheptadine-induced cell cycle arrest were probed by western blot analysis. Cyproheptadine had a potent inhibitory effect on the proliferation of HepG2 and Huh-7 cells but minimal toxicity in normal hepatocytes. Cyproheptadine induced cell cycle arrest in HepG2 cells in the G1 phase and in Huh-7 cells at the G1/S transition. The Cyproheptadine-induced G1 arrest in HepG2 cells was associated with an increased expression of HBP1 and p16, whereas the G1/S arrest in Huh-7 cells was associated with an increase in p21 and p27 expression and a dramatic decrease in the phosphorylation of the retinoblastoma protein. Additionally, Cyproheptadine elevated the percentage of Huh-7 cells in the sub-G1 population, increased annexin V staining for cell death, and raised the levels of PARP and its cleaved form, indicating induction of apoptosis. Finally, Cyproheptadine-mediated cell cycle arrest was dependent upon the activation of p38 MAP kinase in HepG2 cells and the activation of both p38 MAP kinase and CHK2 in Huh-7 cells. Our results demonstrate that a non-classical p38 MAP kinase function, regulation of cell cycle checkpoints, is one of the underlying mechanisms promoted by Cyproheptadine to suppress the proliferation of HCC cells. These results provide evidence for the drug’s potential as a treatment option for liver cancer.

  • abstract 4566a effect of the anti histaminic Cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms
    Cancer Research, 2014
    Co-Authors: Chengda Hsu, Yu Min Feng, Syueyi Chen, Jingwen Feng
    Abstract:

    Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide; however, current chemotherapeutic drugs for hepatocellular carcinoma (HCC) are either poorly effective or expensive. The majority of patients can9t have good outcomes by taking these drugs. Currently, we had a breakthrough finding in a case report of two patients with advanced HCC. We found one had complete remission of liver tumors, one had decrease of their alpha-fetoprotein levels and that both their lung metastasis had complete remission after the concomitant use of thalidomide and Cyproheptadine. In light of a previous study that Cyproheptadine affects the cell cycle and impedes leukemia cell growth by suppressing the action of transcription factor of cyclin D, we assume that Cyproheptadine is the key factor in this treatment. Therefore, the purpose of this study was to investigate whether Cyproheptadine inhibits HCC cell growth by impeding cancer cell cycle and to explore the molecular mechanisms of Cyproheptadine-induced cell cycle arrest. First, we confirmed that Cyproheptadine had inhibition effect on two HCC cell lines, HepG2 and Huh-7, by cell viability assay. Besides, to explore how Cyproheptadine affects HCC cell cycle we analyzed DNA content by flow cytometry and found cell cycle arrest at the G1 to S transition in HepG2 cells and at the S to G2 transition in Huh-7 cells. Finally, we investigated the mechanism of Cyproheptadine-induced cell cycle arrest using western blot analysis. Interestingly, our results showed that Cyproheptadine promoted P38 activation by phosphorylation than subsequently stabilized P16 and caucused hypophosphorylation of Rb in HepG2 cells. On the other hand, Cyproheptadine not only promoted P38 activation but also activated ATM/Chk2 pathway to stabilize P21 in Huh-7 cells. These novel results demonstrated that Cyproheptadine suppressed HCC cells through the Non-classical P38 MAP Kinase Functions: Cell Cycle Checkpoints and ATM/Chk2 pathway, and provided a potential treatment option in HCC. Citation Format: Cheng-Da Hsu, Yu-Min Feng, Syue-Yi Chen, Jing-Wen Feng. Effect of the anti-histaminic Cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4566A. doi:10.1158/1538-7445.AM2014-4566A

  • unexpected remission of hepatocellular carcinoma hcc with lung metastasis to the combination therapy of thalidomide and Cyproheptadine report of two cases and a preliminary hcc cell line study
    Case Reports, 2012
    Co-Authors: Yu Min Feng, Chinwen Feng, Solomon Chihcheng Chen, Chengda Hsu
    Abstract:

    We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and Cyproheptadine. The use of Cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that Cyproheptadine effectively reduced the viability of two HCC cell lines.