Cacalol Acetate as Anticancer Agent: Antiproliferative, Pro-Apoptotic, Cytostatic, and Anti-Migratory Effects

Author:

Rostro-Alonso Gareth Omar1,Castillo-Montoya Alejandro Israel1,García-Acosta Juan Carlos1,Aguilar-Llanos Erick Fernando2,Quintas-Granados Laura Itzel3ORCID,Villegas-Vazquez Edgar Yebrán1,García-Aguilar Rosario4ORCID,Porras-Vázquez Samantha Andrea1,Bustamante-Montes Lilia Patricia5,Alvarado-Sansininea Jesús J.6,Jiménez-Estrada Manuel6ORCID,Cariño-Calvo Lizbeth7,Carmen Manuel González-del8ORCID,Cortés Hernán9ORCID,Leyva-Gómez Gerardo10ORCID,Figueroa-González Gabriela1ORCID,Reyes-Hernández Octavio Daniel1ORCID

Affiliation:

1. Laboratorio de Farmacogenética, Unidad Multidisciplinaria de Investigación Experimental Zaragoza, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Esquina Fuerte de Loreto, Iztapalapa, Mexico City 09230, Mexico

2. Laboratorio de Biología Molecular del Cáncer, Unidad Multidisciplinaria de Investigación Experimental Zaragoza, Facultad de Estudios Superiores-Zaragoza, Universidad Nacional Autónoma de México, Iztapalapa, Mexico City 09230, Mexico

3. Colegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Calle Dr. García Diego 168, Doctores, Cuauhtémoc, Mexico City 06720, Mexico

4. Laboratorio de Citometría de Flujo y Hematología, Diagnóstico Molecular de Leucemias y Terapia Celular (DILETEC), Gustavo A. Madero, Mexico City 06350, Mexico

5. Coordinacion de Investigacion, Centro Universitario Siglo XXI, Edo. de Mex, Mexico City 03100, Mexico

6. Laboratorio 2–10, Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

7. Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba 94340, Mexico

8. Facultad de Medicina, Universidad Veracruzana, Ciudad Mendoza 94740, Mexico

9. Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico

10. Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

Abstract

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, which has not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA’s antiproliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent indole-3-carbinol (I3C) was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migration and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA’s lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C.

Funder

PAPIIT

Dirección General de Asuntos del Personal Académico (DGAPA) from Universidad Nacional Autónoma de Mexico

Publisher

MDPI AG

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