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Article

Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model

by
Juan Carlos García-Acosta
1,†,
Alejando Israel Castillo-Montoya
1,†,
Gareth Omar Rostro-Alonso
1,†,
Edgar Yebrán Villegas-Vázquez
1,
Laura Itzel Quintas-Granados
2,
Luis Sánchez-Sánchez
3,
Hugo López-Muñóz
3,
Lizbeth Cariño-Calvo
4,
Israel López-Reyes
2,
Lilia Patricia Bustamante-Montes
5,
Gerardo Leyva-Gómez
6,7,
Hernán Cortés
8,
Nadia Judith Jacobo-Herrera
9,
Rosario García-Aguilar
10,
Octavio Daniel Reyes-Hernández
1 and
Gabriela Figueroa-González
1,*
1
Laboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, Mexico
2
Colegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Ciudad de México 07160, Mexico
3
Laboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, Mexico
4
Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba 94340, Mexico
5
Coordinación de Investigación, Centro Universitario Siglo XXI, Edo. de México 03100, Mexico
6
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
7
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Zacatenco, Ciudad de México 07360, Mexico
8
Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra, Ciudad de México 14389, Mexico
9
Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Ciudad de México 14080, Mexico
10
Laboratorio de Citometría de Flujo y Hematología, Diagnóstico Molecular de Leucemias y Terapia Celular (DILETEC), Ciudad de México 07800, Mexico
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2024, 29(18), 4476; https://doi.org/10.3390/molecules29184476
Submission received: 11 August 2024 / Revised: 7 September 2024 / Accepted: 18 September 2024 / Published: 20 September 2024
(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 2nd Edition)
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Abstract

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 Li2CO3 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 IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 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 Li2CO3 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.
Keywords: lithium chloride; lithium carbonate; cervical cancer cells; apoptosis induction; cell cycle arrest; migration inhibition lithium chloride; lithium carbonate; cervical cancer cells; apoptosis induction; cell cycle arrest; migration inhibition

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MDPI and ACS Style

García-Acosta, J.C.; Castillo-Montoya, A.I.; Rostro-Alonso, G.O.; Villegas-Vázquez, E.Y.; Quintas-Granados, L.I.; Sánchez-Sánchez, L.; López-Muñóz, H.; Cariño-Calvo, L.; López-Reyes, I.; Bustamante-Montes, L.P.; et al. Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model. Molecules 2024, 29, 4476. https://doi.org/10.3390/molecules29184476

AMA Style

García-Acosta JC, Castillo-Montoya AI, Rostro-Alonso GO, Villegas-Vázquez EY, Quintas-Granados LI, Sánchez-Sánchez L, López-Muñóz H, Cariño-Calvo L, López-Reyes I, Bustamante-Montes LP, et al. Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model. Molecules. 2024; 29(18):4476. https://doi.org/10.3390/molecules29184476

Chicago/Turabian Style

García-Acosta, Juan Carlos, 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, and et al. 2024. "Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model" Molecules 29, no. 18: 4476. https://doi.org/10.3390/molecules29184476

APA Style

García-Acosta, J. C., Castillo-Montoya, A. I., Rostro-Alonso, G. O., Villegas-Vázquez, E. Y., Quintas-Granados, L. I., Sánchez-Sánchez, L., López-Muñóz, H., Cariño-Calvo, L., López-Reyes, I., Bustamante-Montes, L. P., Leyva-Gómez, G., Cortés, H., Jacobo-Herrera, N. J., García-Aguilar, R., Reyes-Hernández, O. D., & Figueroa-González, G. (2024). Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model. Molecules, 29(18), 4476. https://doi.org/10.3390/molecules29184476

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