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植物源多分子药物对急性白血病肿瘤代谢的调节及其对线粒体功能的影响

Modulation of Tumor Metabolism in Acute Leukemia by Plant-Derived Polymolecular Drugs and Their Effects on Mitochondrial Function.

作者信息

Arévalo Cindy, Carlosama Carolina, Rojas Laura, Cala Mónica P, Hamon Marie-Paule, Friguet Bertrand, Barreto Alfonso, Fiorentino Susana

机构信息

Grupo de Inmunobiología y Biología Celular, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Centro de Metabolómica-MetCore, Universidad de los Andes, Bogotá 111711, Colombia.

出版信息

Molecules. 2025 Apr 16;30(8):1783. doi: 10.3390/molecules30081783.

Abstract

The analysis of tumor metabolism offers promising opportunities for developing new therapeutic strategies. Plant-derived polymolecular drugs can regulate cellular metabolism, making them potential candidates for treatment. This study examined the metabolic effects of plant-derived polymolecular drugs-P2Et, Anamu-SC, and Esperanza-on leukemic cell lines (lymphoid and myeloid types) and primary leukemic blasts. The metabolic analysis included oxidative status, glucose consumption, extracellular acidification, oxygen consumption, mitochondrial dynamics, and untargeted metabolomics. Additionally, the effect of co-treatment with conventional chemotherapeutic drugs was investigated. Results showed that P2Et and Anamu-SC reduced the viability and proliferation of all tumor cell lines, exhibiting antioxidant effects. Anamu-SC decreased reactive oxygen species levels in lymphoid tumor cells. Mitochondrial activity was selectively affected by the plant-derived polymolecular drugs, with Anamu-SC and Esperanza causing more significant, potentially reversible damage compared to P2Et. Anamu-SC and Esperanza increased levels of phosphatidylcholines and carnitines. The co-administration of plant-derived polymolecular drugs with chemotherapeutics improved the cytostatic efficacy of cytarabine. In conclusion, this research highlights the promising pharmacological activity of Anamu-SC and Esperanza as mitocans for the treatment of acute leukemia. The study emphasizes the practical significance of combining plant-derived polymolecular drugs with conventional chemotherapeutics to enhance their cytostatic efficacy.

摘要

肿瘤代谢分析为开发新的治疗策略提供了广阔的机会。植物源多分子药物可以调节细胞代谢,使其成为潜在的治疗候选药物。本研究考察了植物源多分子药物P2Et、阿纳木-SC和埃斯佩兰萨对白血病细胞系(淋巴样和髓样)及原发性白血病母细胞的代谢影响。代谢分析包括氧化状态、葡萄糖消耗、细胞外酸化、氧消耗、线粒体动力学和非靶向代谢组学。此外,还研究了与传统化疗药物联合治疗的效果。结果表明,P2Et和阿纳木-SC降低了所有肿瘤细胞系的活力和增殖,表现出抗氧化作用。阿纳木-SC降低了淋巴样肿瘤细胞中的活性氧水平。线粒体活性受到植物源多分子药物的选择性影响,与P2Et相比,阿纳木-SC和埃斯佩兰萨造成的损伤更显著,且可能是可逆的。阿纳木-SC和埃斯佩兰萨提高了磷脂酰胆碱和肉碱的水平。植物源多分子药物与化疗药物联合给药提高了阿糖胞苷的细胞生长抑制疗效。总之,本研究突出了阿纳木-SC和埃斯佩兰萨作为线粒体靶向剂治疗急性白血病的潜在药理活性。该研究强调了将植物源多分子药物与传统化疗药物联合使用以提高其细胞生长抑制疗效的实际意义。

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