Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells

Yu, Xinyi; Liu, Feng; Zeng, Lijiang; He, Fang; Zhang, Ruyi; Yan, Shujuan; Zeng, Zongyue; Shu, Yi; Zhao, Chen; Wu, Xingye; Lei, Jiayan; Zhang, Wenwen; Yang, Chao; Wu, Ke; Wu, Ying; An, Lihui; Huang, Shifeng; Ji, Xiaojuan; Chen, Gong; Yuan, Chengfu; Zhang, Linghuan; Feng, Yixiao; Huang, Bo; Liu, Wei; Zhang, Bo; Dai, Zhengyu; Wang, Xi; Liu, Bo; Haydon, Rex C.; Luu, Hue H.; Gan, Hua; He, Tong‐Chuan; Chen, Liqun

doi:10.1159/000490140

Cited by 33 publications

(22 citation statements)

References 69 publications

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“…All experimental procedures were performed by following the approved protocol. Xenograft tumor model was established as previously described 28,29,39,43,62–65 . Briefly, Panc-1 cells were stably tagged with FLuc (firefly luciferase) (Panc-1/FLuc) using the piggyBac system 30,41,60 .…”

Section: Methodsmentioning

confidence: 99%

Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway

Wang

Zhang

et al. 2018

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with <5% five-year survival rate due to late diagnosis, limited treatment options and chemoresistance. There is thus an urgent unmet clinical need to develop effective anticancer drugs to treat pancreatic cancer. Here, we study the potential of repurposing monensin as an anticancer drug for chemo-resistant pancreatic cancer. Using the two commonly-used chemo-resistant pancreatic cancer cell lines PANC-1 and MiaPaCa-2, we show that monensin suppresses cell proliferation and migration, and cell cycle progression, while solicits apoptosis in pancreatic cancer lines at a low micromole range. Moreover, monensin functions synergistically with gemcitabine or EGFR inhibitor erlotinib in suppressing cell growth and inducing cell death of pancreatic cancer cells. Mechanistically, monensin suppresses numerous cancer-associated pathways, such as E2F/DP1, STAT1/2, NFkB, AP-1, Elk-1/SRF, and represses EGFR expression in pancreatic cancer lines. Furthermore, the in vivo study shows that monensin blunts PDAC xenograft tumor growth by suppressing cell proliferation via targeting EGFR pathway. Therefore, our findings demonstrate that monensin can be repurposed as an effective anti-pancreatic cancer drug even though more investigations are needed to validate its safety and anticancer efficacy in pre-clinical and clinical models.

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Section: Methodsmentioning

confidence: 99%

Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway

Wang

Zhang

et al. 2018

Sci Rep

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“…For instance, synergy between niclosamide and imatinib, as well as niclosamide and dasatinib or ponatinib, against CML cells was demonstrated (171). Niclosamide was also found to potentiate the effects of erlotinib against head and neck cancer cells through STAT3 inhibition (172), with erlotinib against human colon cancer lines (173), and with sorafenib against human renal cell cancer cells (174).…”

Section: Clinical Trials: Single Agent and Combination Therapy Approamentioning

confidence: 98%

Repurposing of Kinase Inhibitors for Treatment of COVID-19

et al. 2020

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The outbreak of COVID-19, the pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred an intense search for treatments by the scientific community. In the absence of a vaccine, the goal is to target the viral life cycle and alleviate the lung-damaging symptoms of infection, which can be lifethreatening. There are numerous protein kinases associated with these processes that can be inhibited by FDA-approved drugs, the repurposing of which presents an alluring option as they have been thoroughly vetted for safety and are more readily available for treatment of patients and testing in clinical trials. Here, we characterize more than 30 approved kinase inhibitors in terms of their antiviral potential, due to their measured potency against key kinases required for viral entry, metabolism, or reproduction. We also highlight inhibitors with potential to reverse pulmonary insufficiency because of their anti-inflammatory activity, cytokine suppression, or antifibrotic activity. Certain agents are projected to be dualpurpose drugs in terms of antiviral activity and alleviation of disease symptoms, however drug combination is also an option for inhibitors with optimal pharmacokinetic properties that allow safe and efficacious co-administration with other drugs, such as antiviral agents, IL-6 blocking agents, or other kinase inhibitors.

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“…The GLuc reporter assays were carried out as described [56][57][58]. Briefly, exponentially growing HEK-293 and HCT116 cells were seeded in 12-well cell culture plates and coinfected with different combinations of miR expression vectors and/or the GLuc reporter plasmids.…”

Section: Gaussia Luciferase (Gluc) Reporter Assaymentioning

confidence: 99%

A simplified system for the effective expression and delivery of functional mature microRNAs in mammalian cells

et al. 2019

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MicroRNAs (miRNAs) are~22 nucleotide noncoding RNAs that are involved in virtually all aspects of cellular process as their deregulations are associated with many pathological conditions. Mature miRNAs (mMIRs) are generated through a series of tightly-regulated nuclear and cytoplasmic processing events of the transcribed primary, precursor and mMIRs. Effective manipulations of miRNA expression enable us to gain insights into miRNA functions and to explore potential therapeutic applications. Currently, overexpression of miRNAs is achieved by using chemically-synthesized miRNA mimics, or shRNA-like stem-loop vectors to express primary or precursor miRNAs, which are limited by low transfection efficacy or rate-limiting miRNA processing. To overcome rate-limiting miRNA processing, we developed a novel strategy to express mMIRs which are driven by converging U6/H1 dual promoters. As a proof-of-concept study, we constructed mMIR expression vectors for hsa-miR-223 and hsa-Let-7a-1, and demonstrated that the expressed mMIRs effectively silenced target gene expression, specifically suppressed miRNA reporter activity, and significantly affected cell proliferation, similar to respective primary and precursor miRNAs. Furthermore, these mMIR expression vectors can be easily converted into retroviral and adenoviral vectors. Collectively, our simplified mMIR expression system should be a valuable tool to study miRNA functions and/or to deliver miRNA-based therapeutics.

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Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells

Cited by 33 publications

References 69 publications

Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway

Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway

Repurposing of Kinase Inhibitors for Treatment of COVID-19

A simplified system for the effective expression and delivery of functional mature microRNAs in mammalian cells

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