Cabrera-Licona Ariana, Hernández-Fuentes Gustavo A, Pineda-Urbina Kayim, Hernández-Rangel Alejandra E, Alcalá-Pérez Mario A, Diaz-Martinez Janet, Díaz-Llerenas Uriel, Guzmán-Esquivel José, Montesinos-López Osval A, Casarez-Price Juan C, Del-Toro-Equihua Mario, Zaizar-Fregoso Sergio A, Gamez-Bayardo Sergio, Beas-Guzmán Oscar F, Delgado-Enciso Iván
State Cancerology Institute of Colima, Health Services of the Mexican Social Security Institute for Welfare (IMSS-BIENESTAR), Colima 28085, Colima, Mexico.
Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Colima, Mexico.
Pharmaceuticals (Basel). 2025 Aug 9;18(8):1177. doi: 10.3390/ph18081177.
: (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. : 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. : 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. : 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.
刺果番荔枝（AM），俗称番荔枝或瓜拿纳，长期以来因其据称的抗癌特性而被用于传统医学。然而，评估其与传统抗肿瘤药物（ADs）潜在增强或相加作用的科学研究仍然有限。本研究旨在评估刺果番荔枝水提取物单独及与标准抗肿瘤药物联合使用对癌细胞系的细胞毒性作用，同时评估其对健康细胞的安全性。此外，我们使用计算机模拟建模探索了刺果番荔枝代谢物与治疗靶点的潜在分子相互作用。：将刺果番荔枝水提取物（125和250μg/mL）分别作用于两种癌细胞系——MDA-MB-231（人三阴性乳腺癌）和TC-1（小鼠HPV16阳性癌）——以及健康人白细胞和非致瘤性小鼠肺细胞系。使用Alamar Blue™ 检测法评估细胞活力。评估了刺果番荔枝与多种一线抗肿瘤药物的联合作用。使用Molegro Virtual Docker进行计算机分子对接，以评估刺果番荔枝代谢物（槲皮素和金丝桃苷）与A2B腺苷受体的相互作用。此外，分析了13种抗肿瘤药物的理化性质，以探索其与细胞毒性结果的相关性。：单独使用刺果番荔枝水提取物在癌细胞和健康细胞类型中均表现出低细胞毒性。然而，当与抗肿瘤药物联合使用时，在评估浓度下，它增强了对癌细胞的细胞毒性作用，同时使健康细胞免受损伤。对接研究表明，槲皮素和金丝桃苷（刺果番荔枝水提取物中的主要代谢物）与A2B受体之间存在强烈相互作用，为观察到的效应提供了可能的机制解释。：刺果番荔枝水提取物可能作为一种化学调节剂，增强传统抗肿瘤药物对癌细胞的作用，同时保持正常细胞活力。这些发现鼓励进一步对刺果番荔枝作为综合肿瘤学中的辅助药物进行临床前探索。
