Lithium-Induced Modulation of Proliferation and Apoptosis in an In Vitro Model of Colorectal Cancer
Edgar Yebrán Villegas-Vázquez1, Ximena Paola Becerril-Vigueras2, Gerardo Leyva-Gómez3
1Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de Mexico, Ciudad de Mexico 09230, Mexico.
Lithium compounds like lithium carbonate and lithium chloride show promise in reducing colorectal cancer (CRC) cell growth and self-renewal. These agents induce apoptosis through a caspase-independent pathway, suggesting potential as low-toxicity adjuvant therapies for CRC.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Colorectal cancer (CRC) is a significant global health burden characterized by uncontrolled cell proliferation.
- Current treatments for CRC can have considerable toxicity, necessitating the exploration of novel therapeutic strategies.
- Lithium compounds have demonstrated various biological activities, prompting investigation into their anti-cancer potential.
Purpose of the Study:
- To evaluate the cytotoxic and molecular effects of lithium carbonate (Li2CO3) and lithium chloride (LiCl) on colorectal cancer (CRC) cell lines.
- To assess the impact of lithium exposure on CRC cell proliferation, self-renewal capacity, and apoptosis.
- To investigate the underlying molecular mechanisms, including effects on Wnt/β-catenin signaling and apoptosis pathways.
Main Methods:
- Cytotoxicity was assessed using viability assays (IC50 determination) and lactate dehydrogenase (LDH) assays.
- Cell proliferation and self-renewal were evaluated through colony-forming efficiency (CFE) assays and phenotypic analysis (holoclones, meroclones, paraclones).
- Apoptosis was confirmed using TUNEL and Annexin-V/IP assays, while Western blotting analyzed protein expression (e.g., p-Ser9 GSK-3β, c-Myc, PARP-1, caspase-3).
Main Results:
- Lithium salts exhibited dose-dependent cytotoxicity against CRC cell lines (HCT-116 and SW-620), with HCT-116 being more sensitive.
- Long-term lithium exposure reduced CRC cell proliferation, colony formation, and stem-like characteristics.
- Apoptosis was induced in over 40% of CRC cells via a caspase-independent pathway, with cell-specific modulation of GSK-3β and PARP-1 cleavage observed.
Conclusions:
- Lithium compounds selectively reduce colorectal cancer cell viability and impair stem-like properties.
- Lithium salts induce apoptosis through a caspase-independent mechanism in CRC cells.
- These findings support the potential of lithium-based compounds as low-toxicity adjuvant agents for colorectal cancer therapy.
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