Ivermectin inhibits HSP27 and potentiates efficacy of oncogene targeting in tumor models

Nappi, Lucia; Aguda, A.H.; Nakouzi, Nader Al; Lelj-Garolla, Barbara; Beraldi, Eliana; Lallous, Nada; Thi, Marisa; Moore, Susan C.; Fazli, Ladan; Battsogt, Dulguun; Stief, Sophie M.; Ban, Fuqiang; Nguyen, Nham T.; Saxena, Neetu; Dueva, Evgenia V.; Zhang, Fan; Yamazaki, Takeshi; Zoubeidi, Amina; Cherkasov, Artem; Brayer, G.D.; Gleave, Martin

doi:10.1172/jci130819

Cited by 40 publications

(46 citation statements)

References 58 publications

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“…Prostate cancer is a malignant tumor derived from prostate epithelial cells, and its morbidity is second only to that of lung cancer among men in Western countries [ 49 ]. In Nappi's experiment, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel [ 50 ]. Interestingly, IVM also restored the sensitivity of the triple-negative breast cancer to the anti-estrogen drug tamoxifen [ 36 ], which also implies the potential for IVM to be used in endocrine therapy.…”

Section: The Role Of Ivm In Different Cancersmentioning

confidence: 99%

“…Nishio found that IVM could significantly inhibit the proliferation of H1299 lung cancer cells by inhibiting YAP1 activity [ 43 ]. Nappi's experiment also proved that IVM combined with erlotinib to achieved a synergistic killing effect by regulating EGFR activity and in HCC827 lung cancer cells [ 50 ]. In addition, IVM could reduce the metastasis of lung cancer cells by inhibiting EMT.…”

Section: The Role Of Ivm In Different Cancersmentioning

confidence: 99%

“…IVM inhibited the activation of EGFR and the downstream ERK/Akt/NF-kappa B signaling pathway to downregulate the expression of P-gp. Earlier, we mentioned the role of IVM in docetaxel-resistant prostate cancer [ 50 ] and gemcitabine-resistant cholangiocarcinoma [ 44 ]. These results indicated the significance of applying IVM for the treatment of chemotherapy patients with MDR.…”

Section: Anticancer Effect Of Ivm Through Other Pathwaysmentioning

confidence: 99%

“…Recent studies have found that IVM could be used as an inhibitor of HSP27 phosphorylation to enhance the activity of anti-EGFR drugs in EGFR/HER2- driven tumors. An experiment found that IVM could significantly enhance the inhibitory effects of erlotinib and cetuximab on lung cancer and colorectal cancer [ 50 ]. Earlier, we mentioned that IVM combined with conventional chemotherapeutic drugs such as cisplatin [ 60 ], paclitaxel [ 59 ], daunorubicin and cytarabine [ 51 ], or with targeted drugs such as dasatinib [ 53 ] and dapafenib [ 73 ] shows great potential for cancer treatment.…”

Section: Anticancer Effect Of Ivm Through Other Pathwaysmentioning

confidence: 99%

“…It has been widely used in humans for many years, and its various pharmacological properties, including long- and short-term toxicological effects and drug metabolism characteristics are very clear. In healthy volunteers, the dose was increased to 2 mg/Kg, and no serious adverse reactions were found, while tests in animals such as mice, rats, and rabbits found that the median lethal dose (LD50) of IVM was 10-50 mg/Kg [ 112 ] In addition, IVM has also been proven to show good permeability in tumor tissues [ 50 ]. Unfortunately, there have been no reports of clinical trials of IVM as an anticancer drug.…”

Section: Summary and Outlooksmentioning

confidence: 99%

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Ivermectin, a potential anticancer drug derived from an antiparasitic drug

Tang

Wang

et al. 2021

Pharmacological Research

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Graphical abstract Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. This may be related to the regulation of multiple signaling pathways by ivermectin through PAK1 kinase. On the other hand, ivermectin promotes programmed cancer cell death, including apoptosis, autophagy and pyroptosis. Ivermectin induces apoptosis and autophagy is mutually regulated. Interestingly, ivermectin can also inhibit tumor stem cells and reverse multidrug resistance and exerts the optimal effect when used in combination with other chemotherapy drugs.

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Section: The Role Of Ivm In Different Cancersmentioning

confidence: 99%

Section: The Role Of Ivm In Different Cancersmentioning

confidence: 99%

Section: Anticancer Effect Of Ivm Through Other Pathwaysmentioning

confidence: 99%

Section: Anticancer Effect Of Ivm Through Other Pathwaysmentioning

confidence: 99%

Section: Summary and Outlooksmentioning

confidence: 99%

See 3 more Smart Citations

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

Tang

Wang

et al. 2021

Pharmacological Research

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SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells

Desiderio

et al. 2020

J Mass Spectrom

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The antiparasitic agent ivermectin offers more promises to treat a diverse range of diseases. However, a comprehensive proteomic analysis of ivermectin‐treated ovarian cancer (OC) cells has not been performed. This study sought to identify ivermectin‐related proteomic profiling and molecular network alterations in human OC cells. Stable isotope labeling with amino acids in cell culture (SILAC)‐based quantitative proteomics was used to study the human OC TOV‐21G cells. After TOV‐21G cells underwent 10 passages in SILAC‐labeled growth media, TOV‐21G cells were treated with 10 ml of 20 μmol/L ivermectin in cell growing medium for 24 h. The SILAC‐labeled proteins were digested with trypsin; tryptic peptides were identified with mass spectrometry (MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to mine signaling pathway alterations with ivermectin‐related proteins in TOV‐21G cells. Gene ontology (GO) analysis was used to explore biological functions of ivermectin‐related proteins, including biological processes (BPs), cellular components (CCs), and molecular functions (MFs). The protein‐protein interaction network was analyzed with molecular complex detection (MCODE) to identify hub modules. In total, 4,447 proteins were identified in ivermectin‐treated TOV‐21G cells. KEGG analysis revealed 89 statistically significant signaling pathways. Interestingly, the clustering analysis of these pathways showed that ivermectin was involved in various cancer pathogenesis processes, including modulation of replication, RNA metabolism, and translational machinery. GO analysis revealed 69 statistically significant CCs, 87 MFs, and 62 BPs. Furthermore, MCODE analysis identified five hub modules, including 147 hub molecules. Those hub modules involved ribosomal proteins, RNA‐binding proteins, cell‐cycle progression‐related proteins, proteasome subunits, and minichromosome maintenance proteins. These findings demonstrate that SILAC quantitative proteomics is an effective method to analyze ivermectin‐treated cells, provide the first ivermectin‐related proteomic profiling and molecular network alterations in human OC cells, and provide deeper insights into molecular mechanisms and functions of ivermectin to inhibit OC cells.

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Ivermectin as a potential therapeutic strategy for glioma

Hu,

Ju,

Zhang

2023

J of Neuroscience Research

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Ivermectin (IVM), a semi‐synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor‐specific proteins, inducing programmed cell death, and modulation of tumor‐related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.

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Ivermectin inhibits HSP27 and potentiates efficacy of oncogene targeting in tumor models

Abstract: The University of British Columbia has granted patents on the HSP27 antisense OGX-427 (PCT/CA03/01588), listing MG as an inventor. A patent application (62/756,707) has been submitted on ivermectin analogs for the treatment of cancer, listing MG as inventor.

Cited by 40 publications

References 58 publications

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells

Ivermectin as a potential therapeutic strategy for glioma

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