Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer

Chen, Jiajie; Zhang, Lína; Cai, Nan; Zhang, Zhen; Ji, Kunmei

doi:10.3892/or.2019.7229

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…If intracellular ROS is responsible for the decreased proliferation, cell viability would be increased in the presence of NAC. As previously reported, treatment with 100 μM NAC increased the proliferation of RF-EMF-unexposed Huh7 cells and ASCs by 9% and 12%, respectively due to its anti-oxidation effect 33,34 . Interestingly, when both Huh7 cells and ASCs were pre-treated with NAC, cell number was increased by 49% in Huh7 and 42% in ASCs following the exposure to 1.7 GHz RF-EMF/LTE for 72 h at 2 SAR, compared with the cells only exposed to RF-EMF without NAC (Fig.…”

Section: Continuous Exposure To 17 Ghz Lte Rf-emf Delayed Cell Cyclesupporting

confidence: 80%

Continuous Exposure to 1.7 GHz LTE Electromagnetic Fields Increases Intracellular Reactive Oxygen Species to Decrease Human Cell Proliferation and Induce Senescence

Choi

Min

Jeon

et al. 2020

Sci Rep

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Due to the rapid development of mobile phone technology, we are continuously exposed to 1.7 GHz LTE radio frequency electromagnetic fields (RF-EMFs), but their biological effects have not been clarified. Here, we investigated the non-thermal cellular effects of these RF-EMFs on human cells, including human adipose tissue-derived stem cells (ASCs), Huh7 and Hep3B liver cancer stem cells (CSCs), HeLa and SH-SY5Y cancer cells, and normal fibroblast IMR-90 cells. When continuously exposed to 1.7 GHz LTE RF-EMF for 72 h at 1 and 2 SAR, cell proliferation was consistently decreased in all the human cells. The anti-proliferative effect was higher at 2 SAR than 1 SAR and was less severe in ASCs. The exposure to RF-EMF for 72 h at 1 and 2 SAR did not induce DNA double strand breaks or apoptotic cell death, but did trigger a slight delay in the G1 to S cell cycle transition. Cell senescence was also clearly observed in ASC and Huh7 cells exposed to RF-EMF at 2 SAR for 72 h. Intracellular ROS increased in these cells and the treatment with an ROS scavenger recapitulated the anti-proliferative effect of RF-EMF. These observations strongly suggest that 1.7 GHz LTE RF-EMF decrease proliferation and increase senescence by increasing intracellular ROS in human cells. The development of wireless communication technology has made our life efficient and convenient. In return, we are continuously exposed to radio frequency electromagnetic fields (RF-EMFs) and environmental exposure to RF-EMFs has steadily increased. The International Agency for Research on Cancer (IARC) classified radiofrequency electromagnetic fields as Group 2B carcinogens in 2011 1,2. However, biological studies have not consistently supported or clarified the carcinogenic effect of RF-EMF. A review of 2012 suggested that the currently available data did not show genotoxic effect from RF-EMF 3. Two recent animal studies by the US National Toxicology Program 4,5 and the Ramazzini Institute 6 investigated the carcinogenic potential of long-term exposure to RF-EMFs associated with mobile phones. The International Commission on Non-ionizing Radiation Protection (ICNRP) evaluated these two reports and recently announced that the conclusions concerning the carcinogenic potential of RF-EMFs could not be drawn due to the technical limitations of the studies 7. On the other hand, a recent report showed that rats exposed from prenatal life until natural death to 1.8 GHz global system for mobile (GSM) communication increased the incidence of heart malignant schwannoma among males exposed at the highest dose 8. Thus, the carcinogenic effects of RF-EMF are still unclear.

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Section: Continuous Exposure To 17 Ghz Lte Rf-emf Delayed Cell Cyclesupporting

confidence: 80%

Continuous Exposure to 1.7 GHz LTE Electromagnetic Fields Increases Intracellular Reactive Oxygen Species to Decrease Human Cell Proliferation and Induce Senescence

Choi

Min

Jeon

et al. 2020

Sci Rep

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“…Recently, it has been demonstrated that PMZ inhibits P-gp, increasing apoptosis, as well as the expression of pRB and phosphorylated H2AX in KBV20 cells (425). Finally, Chen et al (426) reported that PMZ induces a reversible inhibition of proliferation in liver cancer and has an additive activity with sorafenib, which indicates the potential of pimozide as an adjuvant anticancer therapy.…”

Section: Pimozide (Pmz)mentioning

confidence: 98%

New drugs are not enough‑drug repositioning in oncology: An update

Armando

Gómez

2020

Int J Oncol

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Drug repositioning refers to the concept of discovering novel clinical benefits of drugs that are already known for use treating other diseases. The advantages of this are that several important drug characteristics are already established (including efficacy, pharmacokinetics, pharmacodynamics and toxicity), making the process of research for a putative drug quicker and less costly. Drug repositioning in oncology has received extensive focus. The present review summarizes the most prominent examples of drug repositioning for the treatment of cancer, taking into consideration their primary use, proposed anticancer mechanisms and current development status.

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“…For example, pimozide induced ROS generation by downregulating the expression of the antioxidant enzyme catalase to suppress osteosarcoma and prostate cancer [ 166 , 167 ]. Moreover, recently, the ability of ROS generation to suppress hepatocellular carcinoma cells has been reported [ 168 ]. However, to date, pimozide has not been investigated in clinical trials to clarify the antitumor activity.…”

Section: Repurposed Drug-regulated Ros Homeostasis As a Novel Cancer Therapeutics In Oncologymentioning

confidence: 99%

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy

Wang

Sun

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Despite tremendous resources being invested in prevention and treatment for cancer, cancer remains a leading cause of human deaths and brings a heavy burden to humans worldwide. Chemotherapy remains the key treatment for cancer therapy, but it produces harmful side effects. Meanwhile, the process of de novo development of new anticancer drugs generally needs increasing cost, long development cycle, and high risk of failure. The use of ROS-based repurposed drugs may be one of the promising ways to overcome current cancer treatment challenges. In this review, we briefly introduce the source and regulation of ROS and then focus on the status of repurposed drugs based on ROS regulation for cancer therapy and propose the challenges and direction of ROS-mediated cancer treatment.

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Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer

Cited by 10 publications

References 32 publications

Continuous Exposure to 1.7 GHz LTE Electromagnetic Fields Increases Intracellular Reactive Oxygen Species to Decrease Human Cell Proliferation and Induce Senescence

Continuous Exposure to 1.7 GHz LTE Electromagnetic Fields Increases Intracellular Reactive Oxygen Species to Decrease Human Cell Proliferation and Induce Senescence

New drugs are not enough‑drug repositioning in oncology: An update

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy

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