niclosamide

Our research revealed comprehensive metabolic alterations in gastric cancer, including upregulated lactate metabolism that promotes tumorigenesis via the lactate shuttle. Niclosamide targets the m6A methylation regulatory protein YTHDF2, which influences genes related to metabolism, indicating its potential as a prospective treatment for GC.

Tyrosine kinase inhibitors (TKIs), such as sunitinib and sorafenib, are standard treatments for renal cell carcinoma (RCC). RNA sequencing (RNA-seq) and bioinformatic analyses showed that niclosamide modulated critical pathways, including BRIP1- and FANCA-mediated DNA repair and E2F2-regulated cell cycle progression. These findings provide proof-of-concept that niclosamide enhances TKI efficacy through modulation of DNA repair and cell cycle pathways, supporting the rationale for DNA damage response (DDR)-targeted combination strategies in RCC.

Given the reduced ATP-generating capacity of SDHB -KO cells, we hypothesized they would be uniquely sensitive to futile cycle induction with mitochondrial ionophores (2,4-Dinitrophenol (2-DNP), BAM15, Niclosamide, Nitazoxanide). Thus, the accumulation of succinate in SDH-deficient tumors inhibits KDM4 activity, impairs DNA repair and yields enhanced susceptibility to Ym155-induced reactive oxygen species (ROS) generation. The identified intrinsic susceptibilities of SDHB -deficient cancers has the potential to be therapeutically leveraged.

PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.

Herein, we developed a mito-specific "Trojan Horse" nanoplatform (2-pN@LNPs) coloaded with Niclosamide (Nic) and 2-deoxy-d-glucose (2-DG) to attack key metabolism pathways and synergistically ignite pyroptosis for restoring antitumor immunity. Moreover, the synergistic treatment regimen can promote cytotoxic and helper T cells (CD8+/CD4+ T cells) recruitment and M1-type macrophage polarization, facilitating the establishment of a boost in immunological memory to prevent recurrence and metastasis. Overall, this work provides a robust strategy targeting metabolism through mitochondrial uncoupling and glycolysis inhibition, which can effectively improve the antitumor effect, inhibit lung metastasis, and help modulate antitumor immunity.

Therapeutic options are minimal, with nitazoxanide (NTZ) being the only drug available, despite its constrained effectiveness...Mice were immunosuppressed using dexamethasone, infected with C. parvum oocysts, and administered NTZ or NICLO...These findings highlight NICLO's dual therapeutic potential, which effectively targets C. parvum infection and mitigates its tumorigenic effects by disrupting key signaling pathways involved in ileocecal cancer progression. This study provides novel insights into NICLO's chemotherapeutic efficacy in managing cryptosporidiosis and its associated oncogenic potential.

In addition, the LEF1 inhibitor niclosamide increased ovarian cancer sensitivity to Cisplatin and PARPi in patient-derived organoids and Niraparib-resistant cell lines. These findings indicate that LEF1 is a potential therapeutic target for overcoming resistance to chemotherapy based on platinum and PARPi in EOC.

Importantly, pharmacological induction of autophagy increases CRC cell sensitivity to chemotherapeutic agents (5-fluorouracil and oxaliplatin) and attenuates high glucose-induced tumorigenic behaviors...Furthermore, enhancing autophagy via the autophagy inducer rapamycin significantly suppressed high glucose-induced tumor formation in a CRC xenograft mouse model. In addition, we identified niclosamide (NC), a repurposed antihelminthic agent, and its derivative niclosamide ethanolamine (NEN), as potential G9a inhibitors and autophagy inducers. NEN dose-dependently suppressed high glucose-activated oncogenic signaling pathways, including β-catenin, c-Myc, STAT3, G9a, and cyclin D1, while restoring autophagy activity. Collectively, our in vitro and in vivo findings strongly support that enhancing autophagy represents a multifaceted strategy to alleviate hyperglycemia, inhibit G9a-mediated signaling, increase chemosensitivity, and suppress high glucose-driven CRC tumorigenesis.

Valine-niclosamide improves upon niclosamide's poor solubility and oral bioavailability, increasing its utility for a variety of therapeutic uses. Further study of valine-niclosamide in advanced HCC and in other cancers or diseases is warranted.

This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide's therapeutic potential in oncology, as well as its possible applications in cancer treatment.

Niclosamide-induced apoptosis was inhibited by an autophagy initiator (3-methyladenine) but significantly enhanced by chloroquine, an autophagy blocker. In conclusion, blocking autophagy is cytotoxic and promotes niclosamide-induced apoptosis. Phosphorylated JNK is identified for the first time as a common regulator of niclosamide-induced autophagy and apoptosis, acting through ROS-dependent or ROS-independent pathways.

In this study, the changes that the combination of the HDAC inhibitor Valproic acid (VPA) and Wnt/β-Catenin pathway inhibitor Niclosamide (Niclo) may cause in cytotoxicity, apoptosis, cell cycle, and EMT mechanisms in lung cancer cell lines (A549 and H1299) were examined...As a result of the analyses, it was seen that VPA + Niclo combination therapy could play a critical role in preventing the acquisition of the mesenchymal phenotype, reducing cell migration and invasion ability, and preventing tumor cell survival and resistance to apoptosis. In conclusion, it was determined that VPA + Niclo combination treatment shows anticancer activity in lung cancer cells and is a promising approach that may have a synergistic effect in inhibiting EMT.