Abstract
Annona purpurea Moc. & Sessé ex Dunal, Annonaceae, is a plant species found in the Mexican Pacific coast. Based on ethnomedical information, different parts of the A. purpurea species are used for medicinal purposes. A recent study revealed the existence of five new acetogenins with cytotoxic activity in the nanomolar range, being annopurpuricin A its main component with an GI50 value in a low/subnanomolar range (HeLa 0.063 nM, 72 h). Therefore, an in vivo study was proposed to establish dosage parameters for the use of annopurpuricin A, as a powerful antitumor substance of natural origin. First, the calculation of LD50 in a healthy murine model was performed to establish the dose range to be used in the tumor model. In vitro cytotoxicity on TC-1 cells and ex vivo toxicity on human lymphocytes were also evaluated. A murine model of HPV-related cancer was used to parallel assess tumor growth, survival, toxicity, and the presence/absence of biochemical and histopathological damage in the liver or kidneys. In addition, hematological and clinical parameters were obtained from samples taken from mice subjected to the study. Annopurpuricin A at a dose of 125 µg/kg/72 h showed characteristics that would allow it to be incorporated into future treatments, achieving a tumor reduction of 60% at day 18 in comparison to the untreated control. Annopurpuricin A at 125 µg/kg/72 h showed a similar effect to that obtained with cisplatin but with a dose 40 times lower. Annopurpuricin A was well tolerated and showed a potent antitumor effect without kidney damage. Also, it was 20 times less cytotoxic than cisplatin for human normal lymphocytes treated ex vivo. Further studies are needed to evaluate the clinical usefulness of this compound.
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All data supporting the findings of this study are available in the supplementary material.
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Acknowledgements
GA Hernández-Fuentes thanks the financial support from CONACYT for his PhD studies (633738) and to M. Sc. Edith Rodriguez-Garay and Prof. Fernando Galindo-Ortiz for the support obtained for the analysis and interpretation of the clinical and hematological tests carried out in the toxicity experiment.
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GAHF, HPD, and IDE: conceptualization; IGEM, JJDM, SAZF, AEHR, ACGC, JGE, MDM, and IPRS: methodology; IGV and MLMF: formal analysis; GAHF, HPD, and IDE: investigation; IGEM: data curation; GAHF, HPD, and IDE: writing, review, and editing of manuscript. All authors have read and agreed to the published version of the manuscript.
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All animals were handled according to the institutional guidelines of the official Mexican Standard for the Use of Laboratory Animals (NOM-062-ZOO-1999), in addition to the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences of the USA (2011) (de Aluja 2002). All animals were euthanized according to the American Veterinary Medical Association (2013) guidelines for the sacrifice of animals. The Ethics Committee of the Institute of Cancerology of the State of Colima approved the protocol with registration code CEICANCL161015-EVANTIM09.
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Hernández-Fuentes, G.A., Delgado-Enciso, I., Enríquez-Maldonado, I.G. et al. Antitumor Effects of Annopurpuricin A, an Acetogenin from the Roots of Annona purpurea. Rev. Bras. Farmacogn. 34, 111–121 (2024). https://doi.org/10.1007/s43450-023-00467-7
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DOI: https://doi.org/10.1007/s43450-023-00467-7