The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer

Abstract

Ivermectin is an old, common, and classic anti-parasite drug, which has been found to have a broad-spectrum anti-cancer effect on multiple human cancers. This chapter will focus on the anti-cancer effects of ivermectin on ovarian cancer. First, ivermectin was found to suppress cell proliferation and growth, block cell cycle progression, and promote cell apoptosis in ovarian cancer. Second, drug pathway network, qRT-PCR, and immunoaffinity blot analyses found that ivermectin acts through molecular networks to target the key molecules in energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle, to inhibit ovarian cancer growth. Third, the integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, SILAC quantitative proteomics analysis revealed that ivermectin extensively inhibited the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes including those key molecules in energy metabolism pathways, and also those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability. Further, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which is significantly associated with overall survival and clinicopathologic characteristics in ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.

A cellular and molecular biology-based update for ivermectin against COVID-19: is it effective or non-effective?

“…Therefore, targeting these metabolic processes could help develop potential treatments to alleviate the inflammatory response and side effects during COVID-19. Ivermectin has recently been shown to play an important role throughout molecular networks by acting on key enzymes in energy metabolism pathways, particularly glycolysis phosphofructokinase, platelet (PFKP), isocitrate dehydrogenase [NADP (+)] 2 (IDH2) and isocitrate dehydrogenase, [NAD(+)] 3-non-catalytic subunit beta (IDH3B), cytochrome b (CYTB), NADH dehydrogenase 2 (ND2), (ND5) and ubiquinol cytochrome c reductase hinge protein (UQCRH) oxidation of the Krebs cycle Phosphorylation, and monocarboxylate transporter 1 (MCT1) and MCT4 in the lactate shuttle(Zhan and Li 2021 ). Therefore, we hypothesized that ivermectin might have a therapeutic effect on COVID-19 by altering energy metabolic pathways, reducing the inflammatory response, and reducing some of the side effects of COVID-19 (Fig.…”