ArticleScientific reports2022
Sorafenib and nitazoxanide disrupt mitochondrial function and inhibit regrowth capacity in three-dimensional models of hepatocellular and colorectal carcinoma.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Synergistic mechanisms and clinical translation of regorafenib combination therapies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- Inhibition of colorectal carcinogenesis by sunitinib malate: disruption of the IL-6/STAT3/c-MYC/TWIST/MMP2 autocrine signaling axis.Discover oncology · 2025Article
- An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.Scientific reports · 2024Article
- Spheroids and organoids derived from colorectal cancer as tools forExploration of targeted anti-tumor therapy · 2024Review
- Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine.Scientific reports · 2023Article
- Nitazoxanide inhibits acetylated KLF5-induced bone metastasis by modulating KLF5 function in prostate cancer.BMC medicine · 2023Article
- Salicylanilides and Their Anticancer Properties.International journal of molecular sciences · 2023Review
- Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.Theranostics · 2023Article
- Three-dimensional heterotypic colorectal cancer spheroid models for evaluation of drug response.Frontiers in oncology · 2023Review
- Exploring oncology treatment strategies with tyrosine kinase inhibitors through advanced 3D models (Review).Medicine internationalReview
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quiescent cancer cells in malignant tumors can withstand cell-cycle active treatment and cause cancer spread and recurrence. Three-dimensional (3D) cancer cell models have led to the identification of oxidative phosphorylation (OXPHOS) as a context-dependent vulnerability. The limited treatment options for advanced hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) metastatic to the liver include the multikinase inhibitors sorafenib and regorafenib. Off-target effects of sorafenib and regorafenib are related to OXPHOS inhibition; however the importance of this feature to the effect on tumor cells has not been investigated in 3D models. We began by assessing global transcriptional responses in monolayer cell cultures, then moved on to multicellular tumor spheroids (MCTS) and tumoroids generated from a CRC patient. Cells were treated with chemotherapeutics, kinase inhibitors, and the OXPHOS inhibitors. Cells grown in 3D cultures were sensitive to the OXPHOS inhibitor nitazoxanide, sorafenib, and regorafenib and resistant to other multikinase inhibitors and chemotherapeutic drugs. Furthermore, nitazoxanide and sorafenib reduced viability, regrowth potential and inhibited mitochondrial membrane potential in an additive manner at clinically relevant concentrations. This study demonstrates that the OXPHOS inhibition caused by sorafenib and regorafenib parallels 3D activity and can be further investigated for new combination strategies.
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