Ramírez-Santos Jesica, Calzada Fernando, García-Hernández Normand, Barbosa Elizabeth, Velázquez Claudia, Valdes Miguel
Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City CP 06720, Mexico.
Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City CP 06725, Mexico.
Int J Mol Sci. 2024 Dec 12;25(24):13355. doi: 10.3390/ijms252413355.
The Annona genus contains some species used in Mexican traditional medicine for the treatment cancer, including . The present study aimed to investigate the anticancer activity of caryophyllene oxide (CO) isolated from using in vivo, in vitro, and in silico approaches. The identification of CO was performed using gas chromatography-mass spectroscopy and NMR methods. Antilymphoma activity was evaluated in male and female Balb/c mice inoculated with U-937 cells. Cytotoxic activity was evaluated using the WST method and flow cytometry was used to determine the type of cell death. Acute oral toxicity was determined, and a molecular docking study was performed using target proteins associated with cancer, including, HMG-CoA, Bcl-2, Mcl-1, and VEGFR-2. Results showed that CO exhibited significant antilymphoma and cytotoxic activities, and its effects were comparable to MTX. In addition, flow cytometry showed that the anticancer activity of CO could be mediated by the induction of late apoptosis and necrosis. The result for the acute oral toxicity of CO was classified in category 4, suggesting it is low risk. Finally, molecular coupling studies showed that CO had more affinity for the enzymes HMG-CoA reductase and Bcl-2. Our study provides evidences that CO is a potential anticancer agent for the treatment of histiocytic lymphoma.
番荔枝属包含一些在墨西哥传统医学中用于治疗癌症的物种，包括……本研究旨在采用体内、体外和计算机模拟方法，研究从……中分离出的氧化石竹烯（CO）的抗癌活性。采用气相色谱-质谱联用和核磁共振方法对CO进行鉴定。在接种U-937细胞的雄性和雌性Balb/c小鼠中评估抗淋巴瘤活性。采用WST法评估细胞毒性活性，并用流式细胞术确定细胞死亡类型。测定急性经口毒性，并使用与癌症相关的靶蛋白（包括HMG-CoA、Bcl-2、Mcl-1和VEGFR-2）进行分子对接研究。结果表明，CO具有显著的抗淋巴瘤和细胞毒性活性，其效果与甲氨蝶呤相当。此外，流式细胞术显示，CO的抗癌活性可能由晚期凋亡和坏死的诱导介导。CO的急性经口毒性结果分类为4类，表明其风险较低。最后，分子偶联研究表明，CO对HMG-CoA还原酶和Bcl-2酶具有更高的亲和力。我们的研究提供了证据，证明CO是治疗组织细胞淋巴瘤的潜在抗癌药物。
