New use for old drugs: The protective effect of atypical antipsychotics on hepatocellular carcinoma

Chen, Vincent Chin Hung; Chan, Hsiao‐Lung; Hsu, Tsai‐Ching; Lu, Mong Liang; Lee, Yi Chen; Lee, Yena; Siow, Jing Yi; McIntyre, Roger S.; Zhou, Aileen; Tzang, Bor‐Show; Lee, Charles Tzu Chi

doi:10.1002/ijc.31980

Cited by 10 publications

(20 citation statements)

References 23 publications

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“…The use of different methods to validate the drug's effects on cancer, in addition to using population-based studies, is recommended because of the aforementioned limitation. We observed that some findings from population-based studies cannot be replicated from cell studies, such as the effect of olanzapine on hepatic cell carcinoma [2]. In this study, we extended our previous dual-model study (population-based study and cell study) [2] to a triple-model study (population-based, cell study, and animal study) to detect the cancer-protective effect of specific drugs.…”

Section: Strengths and Limitationsmentioning

confidence: 92%

“…We observed that some findings from population-based studies cannot be replicated from cell studies, such as the effect of olanzapine on hepatic cell carcinoma [2]. In this study, we extended our previous dual-model study (population-based study and cell study) [2] to a triple-model study (population-based, cell study, and animal study) to detect the cancer-protective effect of specific drugs. The methods provide a research model, and real-world big data may become an essential source of information to discover new possibilities for anticancer drugs.…”

Section: Strengths and Limitationsmentioning

confidence: 92%

“…Investigation of the treatment potential of old drugs in novel indications is currently encouraged through the application of existing health information data (e.g., National Health Insurance [NHI] records) because the long-term real-world data readily provides established effect and safety records [1] However, further validation is often required because of the limitations of observational data, particularly those from routine sources, including unmeasured confounding factors. For example, an epidemiology study of the potential protective effects of olanzapine on hepatic cell carcinoma could not be replicated from cell studies [2].…”

Section: Introductionmentioning

confidence: 99%

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New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Chen

Hsieh

Lin

et al. 2020

Cancers

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(1) Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. (2) Methods: We used data from Taiwan’s National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. (3) Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25–0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. (4) Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

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Section: Strengths and Limitationsmentioning

confidence: 92%

Section: Strengths and Limitationsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Chen

Hsieh

Lin

et al. 2020

Cancers

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“…A new group of 17β‐HSD10 inhibitors are compounds, which are routinely used in clinical practice as drugs for psychiatric disorders. Some atypical antipsychotics were found to have additional effects as anti‐cancer drugs (Chen et al., 2018). The most promising compound is risperidone (18) (Figure 8), an FDA‐approved drug for treating schizophrenia (Marder & Meibach, 1994), which was found to interact with 17β‐HSD10 in a drug screen against the whole genome model of Drosophila melanogaster T7 bacteriophage library (Dilly, Clark, et al., 2017a).…”

Section: Inhibition Of 17β‐hsd10‐aβ Interaction or Enzymatic Activitymentioning

confidence: 99%

Friend or enemy? Review of 17β‐HSD10 and its role in human health or disease

Vinklářová

Schmidt

Benek

et al. 2020

Journal of Neurochemistry

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17β-HSD10 is a mitochondrial enzyme involved in the metabolism of a wide range of substrates, including neurosteroids (He, Dobkin, & Yang, 2019) and sex steroids, maintaining their physiological level (Shafqat et al., 2003). However, it also plays an important role in tRNA processing as a structural component of RNase P (Holzmann et al., 2008). Its abnormal function including inherited mutations leads to disruption in mitochondrial physiology and is thought to be one of the underlying pathological causes for diseases such as Alzheimer's disease (He, Isaacs, & Yang, 2018) and some forms of cancer (Yang, He, & Schulz, 2005). This paper discusses the role of 17β-HSD10 in physiology, as well as its connections to various diseases. The first section gives an overview of 17β-HSD10 structure, localization and physiological functions. In the second section, the role of 17β-HSD10 in disease, specifically in neurodegenerative disorders and cancer are discussed, which together are attracting more and broader interest in this enzyme.

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“…found quetiapine as the protective agent that reduced HCC risk in patients with schizophrenia. Furthermore, quetiapine also inhibited tumor cell growth and invasion ability in HCC in vitro (4). However, the anti-HCC mechanism of quetiapine has not been elucidated.…”

mentioning

confidence: 96%

ERK/AKT Inactivation and Apoptosis Induction Associate With Quetiapine-inhibited Cell Survival and Invasion in Hepatocellular Carcinoma Cells

Lee

Chung

Tan

et al. 2020

In Vivo

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Background/Aim: Quetiapine, an atypical antipsychotic, has been encountered as a potential protective agent to suppress various types of tumor growth. However, the inhibitory mechanism of quetiapine in hepatocellular carcinoma (HCC) still remains unclear. The purpose of present study was to investigate the inhibitory mechanism of quetiapine on cell survival and invasion in HCC. Materials and Methods: Changes of apoptotic signaling, migration/invasion ability, and signaling transduction involved in cell survival and invasion were evaluated with flow cytometry, migration/invasion, and western blot assays. Results: Quetiapine inhibited cell proliferation and migration/invasion in SK-Hep1 and Hep3B cells. Quetiapine induced extrinsic and intrinsic apoptotic pathways. Activation of extracellular signal-regulated kinases (ERK), protein kinase B (AKT), nuclear factor kappa-lightchain-enhancer of activated B cells (NF-ĸB), expression of anti-apoptotic, and metastasis-associated proteins were decreased by quetiapine. Conclusion: The apoptosis induction, the decreased expression of ERK/AKT-mediated anti-apoptotic and the metastasis-associated proteins were associated with quetiapine-inhibited cell survival and invasion in HCC in vitro. Antipsychotic medications are used for the treatment of patients with schizophrenia and other psychotic disorders (1). Recent epidemiological studies have focused on the relationship between cancer risk and the long-term use of antipsychotic drugs in patients with schizophrenia. Long-term antipsychotic treatment did not influence breast cancer risk, whereas risk of gastric or hepatocellular carcinoma (HCC) was reduced with antipsychotic use (2-4). Antipsychotic drugs have been shown to elicit anticancer response in various cancers. Sertindole, the second-generation antipsychotic drug, was presented to induce autophagyassociated apoptosis leading to tumor growth inhibition in breast cancer (5). Aripiprazole, the partial dopamine agonist used for treatment of schizophrenia, not only promoted cell growth inhibition but also increased sensitivity to chemotherapeutic agents in cancer stem cells (6). Quetiapine, the atypical antipsychotic, augments release of neurotransmitters leading to improvement of schizophrenia-negative symptoms (7). In addition to antipsychotic effect, quetiapine as the multifunctional agent has been demonstrated to modulate several biological properties such as anti-inflammation, neuroprotection, and anti-cancer effect (4, 8, 9). Quetiapine was presented to upregulate differentiation of glioma stem cells and enhance anti-glioma efficacy of temozolomide (TMZ) (10). Quetiapine also attenuated breast cancer-induced osteolysis through blocking differentiation of osteoclasts (11). Chen et

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New use for old drugs: The protective effect of atypical antipsychotics on hepatocellular carcinoma

Cited by 10 publications

References 23 publications

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Friend or enemy? Review of 17β‐HSD10 and its role in human health or disease

ERK/AKT Inactivation and Apoptosis Induction Associate With Quetiapine-inhibited Cell Survival and Invasion in Hepatocellular Carcinoma Cells

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