Purpose: Ivermectin is an antiparasitic drug that exhibits antitumor effects in preclinical studies, and as such is currently being repositioned for cancer treatment. However, divergences exist regarding its employed doses in preclinical works. Therefore, the aim of this study was to determine whether the antitumor effects of ivermectin are observable at clinically feasible drug concentrations.
Methods: Twenty-eight malignant cell lines were treated with 5 μM ivermectin. Cell viability, clonogenicity, cell cycle, cell death and pharmacological interaction with common cytotoxic drugs were assessed, as well as the consequences of its use on stem cell-enriched populations. The antitumor in vivo effects of ivermectin were also evaluated.
Results: The breast MDA-MB-231, MDA-MB-468, and MCF-7, and the ovarian SKOV-3, were the most sensitive cancer cell lines to ivermectin. Conversely, the prostate cancer cell line DU145 was the most resistant to its use. In the most sensitive cells, ivermectin induced cell cycle arrest at G-G phase, with modulation of proteins associated with cell cycle control. Furthermore, ivermectin was synergistic with docetaxel, cyclophosphamide and tamoxifen. Ivermectin reduced both cell viability and colony formation capacity in the stem cell-enriched population as compared with the parental one. Finally, in tumor-bearing mice ivermectin successfully reduced both tumor size and weight.
Conclusion: Our results on the antitumor effects of ivermectin support its clinical testing.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00280-020-04041-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of an Efficacious RET PROTAC Degrader with Enhanced Antiproliferative Activity against Resistant Cancer Cells Harboring RET Solvent-Front Mutations.
J Med Chem
December 2024
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Rearranged during transfection (RET) kinase is a validated therapeutic target for various cancers characterized by RET alterations. Although two selective RET inhibitors, selpercatinib and pralsetinib, have been approved by the FDA, acquired resistance through solvent-front mutations has been identified rapidly. Developing proteolysis targeting chimera (PROTAC) targeting RET mutations offers a promising strategy to combat drug resistance.
View Article and Find Full Text PDFpH-Ultrasensitive Membranolytic Polyesters with Alternating Sequence of Ionizable and Hydrophobic Groups for Selective Oncolytic Therapy.
J Am Chem Soc
December 2024
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
Oncolytic therapy, inducing cell death via cell membrane lysis, holds considerable promise in cancer treatment. However, achieving precise control over the structure and function of oncolytic materials for highly selective oncolytic therapy is a key challenge in the context of the subtle differences between tumor and normal tissues/cells. Herein, we report the development of pH-ultrasensitive oncolytic polyesters (pOPs) with an alternating sequence of ionizable and hydrophobic groups.
View Article and Find Full Text PDFNovel PD-L1/VISTA Dual Inhibitor as Potential Immunotherapy Agents.
J Med Chem
December 2024
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Inhibiting the activity of immune checkpoint proteins to reignite the antitumor activity of immune cells has emerged as a pivotal strategy. PD-L1 and VISTA, as critical proteins governing immune regulation, are concurrently upregulated under conditions such as hypoxia. Through a rational drug design process, , a dual-target inhibitor for PD-L1 and VISTA is identified.
View Article and Find Full Text PDFChimeric Peptide-Engineered Polyprodrug Enhances Cytotoxic T Cell Response by Inducing Immunogenic Cell Death and Upregulating Major Histocompatibility Complex Class I.
ACS Nano
December 2024
The Fifth Affiliated Hospital, Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Tumor-specific cytotoxic T cell immunity is critically dependent on effective antigen presentation and sustained signal transduction. However, this immune response is frequently compromised by the inherently low immunogenicity of breast cancer and the deficiency in major histocompatibility complex class I (MHC-I) expression. Herein, a chimeric peptide-engineered stoichiometric polyprodrug (PDPP) is fabricated to potentiate the cytotoxic T cell response, characterized by a high drug loading capacity and precise stoichiometric drug ratio, of which the immunogenic cell death (ICD) inducer of protoporphyrin IX (PpIX) and the epigenetic drug of decitabine (DAC) are condensed into a polyprodrug called PpIX-DAC.
View Article and Find Full Text PDFOne-Pot Synthesis of Oxygen Vacancy-Rich Amorphous/Crystalline Heterophase CaWO Nanoparticles for Enhanced Radiodynamic-Immunotherapy.
Adv Sci (Weinh)
December 2024
New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
Radiodynamic therapy that employs X-rays to trigger localized reactive oxygen species (ROS) generation can tackle the tissue penetration issue of phototherapy. Although calcium tungstate (CaWO) shows great potential as a radiodynamic agent benefiting from its strong X-ray absorption and the ability to generate electron-hole (e-h) pairs, slow charge carrier transfer and fast e-h recombination greatly limit its ROS-generating performance. Herein, via a one-pot wet-chemical method, oxygen vacancy-rich amorphous/crystalline heterophase CaWO nanoparticles (Ov-a/c-CaWO NPs) with enhanced radiodynamic effect are synthesized for radiodynamic-immunotherapy of cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!