Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model
Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt ty...
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2024-09-01
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| author | Juan Carlos García-Acosta Alejando Israel Castillo-Montoya Gareth Omar Rostro-Alonso Edgar Yebrán Villegas-Vázquez Laura Itzel Quintas-Granados Luis Sánchez-Sánchez Hugo López-Muñóz Lizbeth Cariño-Calvo Israel López-Reyes Lilia Patricia Bustamante-Montes Gerardo Leyva-Gómez Hernán Cortés Nadia Judith Jacobo-Herrera Rosario García-Aguilar Octavio Daniel Reyes-Hernández Gabriela Figueroa-González |
| author_facet | Juan Carlos García-Acosta Alejando Israel Castillo-Montoya Gareth Omar Rostro-Alonso Edgar Yebrán Villegas-Vázquez Laura Itzel Quintas-Granados Luis Sánchez-Sánchez Hugo López-Muñóz Lizbeth Cariño-Calvo Israel López-Reyes Lilia Patricia Bustamante-Montes Gerardo Leyva-Gómez Hernán Cortés Nadia Judith Jacobo-Herrera Rosario García-Aguilar Octavio Daniel Reyes-Hernández Gabriela Figueroa-González |
| author_sort | Juan Carlos García-Acosta |
| collection | DOAJ |
| description | Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li<sub>2</sub>CO<sub>3</sub> or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC<sub>50</sub> values on HeLa, SiHa, and HaCaT cells with LiCl and Li<sub>2</sub>CO<sub>3</sub> and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC<sub>50</sub> values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC<sub>50</sub> values for Li<sub>2</sub>CO<sub>3</sub> were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li<sub>2</sub>CO<sub>3</sub> and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li<sub>2</sub>CO<sub>3</sub> arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer. |
| format | Article |
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| spelling | doaj-art-873c372376e942b49ad5d9e5c522c0df2025-08-20T01:55:42ZengMDPI AGMolecules1420-30492024-09-012918447610.3390/molecules29184476Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer ModelJuan Carlos García-Acosta0Alejando Israel Castillo-Montoya1Gareth Omar Rostro-Alonso2Edgar Yebrán Villegas-Vázquez3Laura Itzel Quintas-Granados4Luis Sánchez-Sánchez5Hugo López-Muñóz6Lizbeth Cariño-Calvo7Israel López-Reyes8Lilia Patricia Bustamante-Montes9Gerardo Leyva-Gómez10Hernán Cortés11Nadia Judith Jacobo-Herrera12Rosario García-Aguilar13Octavio Daniel Reyes-Hernández14Gabriela Figueroa-González15Laboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoColegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Ciudad de México 07160, MexicoLaboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoFacultad de Ciencias Químicas, Universidad Veracruzana, Orizaba 94340, MexicoColegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Ciudad de México 07160, MexicoCoordinación de Investigación, Centro Universitario Siglo XXI, Edo. de México 03100, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoLaboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra, Ciudad de México 14389, MexicoUnidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Ciudad de México 14080, MexicoLaboratorio de Citometría de Flujo y Hematología, Diagnóstico Molecular de Leucemias y Terapia Celular (DILETEC), Ciudad de México 07800, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li<sub>2</sub>CO<sub>3</sub> or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC<sub>50</sub> values on HeLa, SiHa, and HaCaT cells with LiCl and Li<sub>2</sub>CO<sub>3</sub> and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC<sub>50</sub> values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC<sub>50</sub> values for Li<sub>2</sub>CO<sub>3</sub> were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li<sub>2</sub>CO<sub>3</sub> and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li<sub>2</sub>CO<sub>3</sub> arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.https://www.mdpi.com/1420-3049/29/18/4476lithium chloridelithium carbonatecervical cancer cellsapoptosis inductioncell cycle arrestmigration inhibition |
| spellingShingle | Juan Carlos García-Acosta Alejando Israel Castillo-Montoya Gareth Omar Rostro-Alonso Edgar Yebrán Villegas-Vázquez Laura Itzel Quintas-Granados Luis Sánchez-Sánchez Hugo López-Muñóz Lizbeth Cariño-Calvo Israel López-Reyes Lilia Patricia Bustamante-Montes Gerardo Leyva-Gómez Hernán Cortés Nadia Judith Jacobo-Herrera Rosario García-Aguilar Octavio Daniel Reyes-Hernández Gabriela Figueroa-González Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model Molecules lithium chloride lithium carbonate cervical cancer cells apoptosis induction cell cycle arrest migration inhibition |
| title | Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model |
| title_full | Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model |
| title_fullStr | Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model |
| title_full_unstemmed | Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model |
| title_short | Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li<sub>2</sub>CO<sub>3</sub>) in an In Vitro Cervical Cancer Model |
| title_sort | unrevealing lithium repositioning in the hallmarks of cancer effects of lithium salts licl and li sub 2 sub co sub 3 sub in an in vitro cervical cancer model |
| topic | lithium chloride lithium carbonate cervical cancer cells apoptosis induction cell cycle arrest migration inhibition |
| url | https://www.mdpi.com/1420-3049/29/18/4476 |
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