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Volume 18
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10.3390/ph18081177
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

In Vitro Evaluation of Annona muricata Leaf Infusion as a Modulator of Antineoplastic Drug-Induced Cytotoxicity in Cancer Cell Lines

by
Ariana Cabrera-Licona
1,†,
Gustavo A. Hernández-Fuentes
1,2,3,†,
Kayim Pineda-Urbina
3,
Alejandra E. Hernández-Rangel
2,
Mario A. Alcalá-Pérez
4,
Janet Diaz-Martinez
5,6,
Uriel Díaz-Llerenas
4,
José Guzmán-Esquivel
7,
Osval A. Montesinos-López
8,
Juan C. Casarez-Price
1,9,
Mario Del-Toro-Equihua
2,
Sergio A. Zaizar-Fregoso
2,
Sergio Gamez-Bayardo
10,
Oscar F. Beas-Guzmán
2 and
Iván Delgado-Enciso
1,2,6,*
1
State Cancerology Institute of Colima, Health Services of the Mexican Social Security Institute for Welfare (IMSS-BIENESTAR), Colima 28085, Colima, Mexico
2
Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Colima, Mexico
3
Faculty of Chemical Sciences, University of Colima, Coquimatlan 28400, Colima, Mexico
4
Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Autonomous University of Zacatecas, Zacatecas 98160, Zacatecas, Mexico
5
Research Center in Minority Institutions, Florida International University (FIU-RCMI), Miami, FL 33199, USA
6
Department of Dietetics & Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University (FIU-RCMI), Miami, FL 33199, USA
7
Clinical Epidemiology Research Unit, Mexican Institute of Social Security, Villa de Alvarez, Colima 28984, Colima, Mexico
8
Faculty of Telematics, University of Colima, Colima 28040, Colima, Mexico
9
Regional University Hospital, Health Services of the State of Colima, Colima 2805, Colima, Mexico
10
Posgrado Integral de Biotecnología, Laboratorio de Investigación y Diagnóstico Microbiológico, Universidad Autónoma de Sinaloa, Culiacán 80010, Sinaloa, Mexico
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceuticals 2025, 18(8), 1177; https://doi.org/10.3390/ph18081177 (registering DOI)
Submission received: 5 June 2025 / Revised: 10 July 2025 / Accepted: 5 August 2025 / Published: 9 August 2025
(This article belongs to the Special Issue Natural Products for Anticancer, Anti-Inflammatory and Antimicrobial Therapies)
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Abstract

Background/Objectives: Annona muricata (AM), commonly known as soursop or guanabana, has long been used in traditional medicine for its purported anticancer properties. However, scientific studies evaluating its potential enhancing or additive effects with conventional antineoplastic drugs (ADs) remain limited. This study aimed to assess the cytotoxic effects of an aqueous AM infusion alone and in combination with standard ADs in cancer cell lines, while also evaluating its safety in healthy cells. Additionally, we explored the potential molecular interactions of AM metabolites with therapeutic targets using silico modeling. Methods: An AM infusion (125 and 250 µg/mL) was tested on two cancer cell lines—MDA-MB-231 (human triple-negative breast cancer) and TC-1 (murine HPV16-positive cancer)—as well as healthy human leukocytes and a non-tumorigenic mouse lung cell line. Cell viability was assessed using the Alamar Blue™ assay. The combined effects of AM with multiple first-line ADs were evaluated. In silico molecular docking was performed with Molegro Virtual Docker to assess the interaction of AM metabolites (quercetin and hyperoside) with the A2B adenosine receptor. Additionally, the physicochemical properties of 13 AD were analyzed to explore correlations with cytotoxic outcomes. Results: AM infusion alone exhibited low cytotoxicity in both cancer and healthy cell types. However, when combined with ADs, it enhanced cytotoxic effects in cancer cells while sparing healthy cells at the evaluated concentrations. Docking studies revealed strong interactions between quercetin and hyperoside (major metabolites in the AM infusion) and the A2B receptor, supporting a possible mechanistic explanation for the observed effects. Conclusions: AM infusion may act as a chemical modulator, potentiating the effects of conventional ADs in cancer cells while preserving normal cell viability. These findings encourage further preclinical exploration of AM as a complementary agent in integrative oncology.
Keywords: guanabana; infusion; adjuvant; traditional medicine; folk medicine; antineoplastic drug; breast cancer guanabana; infusion; adjuvant; traditional medicine; folk medicine; antineoplastic drug; breast cancer
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MDPI and ACS Style

Cabrera-Licona, A.; Hernández-Fuentes, G.A.; Pineda-Urbina, K.; Hernández-Rangel, A.E.; Alcalá-Pérez, M.A.; Diaz-Martinez, J.; Díaz-Llerenas, U.; Guzmán-Esquivel, J.; Montesinos-López, O.A.; Casarez-Price, J.C.; et al. In Vitro Evaluation of Annona muricata Leaf Infusion as a Modulator of Antineoplastic Drug-Induced Cytotoxicity in Cancer Cell Lines. Pharmaceuticals 2025, 18, 1177. https://doi.org/10.3390/ph18081177

AMA Style

Cabrera-Licona A, Hernández-Fuentes GA, Pineda-Urbina K, Hernández-Rangel AE, Alcalá-Pérez MA, Diaz-Martinez J, Díaz-Llerenas U, Guzmán-Esquivel J, Montesinos-López OA, Casarez-Price JC, et al. In Vitro Evaluation of Annona muricata Leaf Infusion as a Modulator of Antineoplastic Drug-Induced Cytotoxicity in Cancer Cell Lines. Pharmaceuticals. 2025; 18(8):1177. https://doi.org/10.3390/ph18081177

Chicago/Turabian Style

Cabrera-Licona, Ariana, Gustavo A. Hernández-Fuentes, Kayim Pineda-Urbina, Alejandra E. Hernández-Rangel, Mario A. Alcalá-Pérez, Janet Diaz-Martinez, Uriel Díaz-Llerenas, José Guzmán-Esquivel, Osval A. Montesinos-López, Juan C. Casarez-Price, and et al. 2025. "In Vitro Evaluation of Annona muricata Leaf Infusion as a Modulator of Antineoplastic Drug-Induced Cytotoxicity in Cancer Cell Lines" Pharmaceuticals 18, no. 8: 1177. https://doi.org/10.3390/ph18081177

APA Style

Cabrera-Licona, A., Hernández-Fuentes, G. A., Pineda-Urbina, K., Hernández-Rangel, A. E., Alcalá-Pérez, M. A., Diaz-Martinez, J., Díaz-Llerenas, U., Guzmán-Esquivel, J., Montesinos-López, O. A., Casarez-Price, J. C., Del-Toro-Equihua, M., Zaizar-Fregoso, S. A., Gamez-Bayardo, S., Beas-Guzmán, O. F., & Delgado-Enciso, I. (2025). In Vitro Evaluation of Annona muricata Leaf Infusion as a Modulator of Antineoplastic Drug-Induced Cytotoxicity in Cancer Cell Lines. Pharmaceuticals, 18(8), 1177. https://doi.org/10.3390/ph18081177

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