ArticlePloS one2015
Lithium Modulates Autophagy in Esophageal and Colorectal Cancer Cells and Enhances the Efficacy of Therapeutic Agents In Vitro and In Vivo.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Lithium-Induced Modulation of Proliferation and Apoptosis in an In Vitro Model of Colorectal Cancer.International journal of molecular sciences · 2025Article
- Review
- Review
- Implication of LAMP proteins and autophagy markers in colorectal cancer aggressiveness.Frontiers in immunology · 2025Article
- Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and LiMolecules (Basel, Switzerland) · 2024Article
- Rocuronium bromide suppresses esophageal cancer via blocking the secretion of C-X-C motif chemokine ligand 12 from cancer associated fibroblasts.Journal of translational medicine · 2023Article
- Lithium: A Promising Anticancer Agent.Life (Basel, Switzerland) · 2023Review
- Lithium in Cancer Therapy: Friend or Foe?Cancers · 2023Review
- Autophagy and necroptosis in cisplatin-induced acute kidney injury: Recent advances regarding their role and therapeutic potential.Frontiers in pharmacology · 2023Review
- Li-Doped Bioactive Ceramics: Promising Biomaterials for Tissue Engineering and Regenerative Medicine.Journal of functional biomaterials · 2022Review
- TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.Journal of hematology & oncology · 2022Review
- The effect of neuropsychiatric medication on pediatric nonalcoholic fatty liver disease.Clinical and translational science · 2022Article
- Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy.Bioactive materials · 2021Article
- Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer.Investigational new drugs · 2021Review
- Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats.Pharmaceutics · 2021Article
- IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma.Journal of clinical medicine · 2020Article
- Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes.Cancers · 2019Review
- circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637.EBioMedicine · 2019Article
- Taxol-Resistant Gene 1 (Txr1) Mediates Oxaliplatin Resistance by Inducing Autophagy in Human Nasopharyngeal Carcinoma Cells.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy.Neural regeneration research · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. However, known pharmacological inhibitors of autophagy could not enhance cytotoxicity. In this study, we have examined two well known, clinically approved autophagy inducers, rapamycin and lithium, for their effects on chemosensitivity in apoptosis incompetent cancer cells. Both lithium and rapamycin were shown to induce autophagosomes in esophageal and colorectal cancer cells by western blot analysis of LC3 isoforms, morphology and FACS quantitation of Cyto-ID or mCherry-GFP-LC3. Analysis of autophagic flux indicates inefficient autophagosome processing in lithium treated cells, whereas rapamycin treated cells showed efficient flux. Viability and recovery was assessed by clonogenic assays. When combined with the chemotherapeutic agent 5-fluorouracil, rapamycin was protective. In contrast, lithium showed strong enhancement of non-apoptotic cell death. The combination of lithium with 5-fluorouracil or oxaliplatin was then tested in the syngenic mouse (balb/c) colorectal cancer model--CT26. When either chemotherapeutic agent was combined with lithium a significant reduction in tumor volume was achieved. In addition, survival was dramatically increased in the combination group (p < 0.0001), with > 50% of animals achieving long term cure without re-occurrence (> 1 year tumor free). Thus, combination treatment with lithium can substantially improve the efficacy of chemotherapeutic agents in apoptosis deficient cancer cells. Induction of compromised autophagy may contribute to this cytotoxicity.
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