Propiedades antitumorales del extracto acuoso de Prosopis strombulifera

The aqueous extract of the Argentinean native plant, Prosopis strombulifera (PsAE), presents cytotoxicity against human cancer cell lines by inducing cytostasis, necrosis and apoptosis; with diminution of clonogenic survival; without genotoxic effects nor oral animal toxicity. Until now, the chemical extract composition and its in vivo antitumoral properties remain unknown; these studies are the aim of the current work. The PsAE was characterized by chemical fingerprinting and the metabolome was identified by tandem UHPLC-PDA-HESI-Q-orbitrap® mass spectrometry. Colorectal tumors were induced by DMH administration and melanomas resulted from B16-F0 S.C. cells injection; then, animals were treated orally with PsEA. To correlate in vivo results with in vitro cytotoxicity, B16-F0 cell were cultured to determine: cell proliferation and viability by dye exclusion assays, MTT and CFSE dilution; cell cycle distribution by flow cytometry; and immunoblotting of p21cip1, PCNA, cleaved caspase 3, cleaved PARP and TUBA1A. Based on UHPLC-OT-MS and PDA analysis, twenty-six compounds were identified, including: 5 simple organic acids, 4 phenolic acids, 4 procyanidins, 11 flavonoids, and 2 oxylipins. On C57BL6 mice, PsAE significantly increases the median survival on colorectal cancer and reduces the final volume and weight of melanomas. Over cultured cells, the treatment induce over-expression of p21, cytostasis by G2/M cell cycle arrest and apoptosis; while, on in vivo melanomas, treatment up-regulates p21 and slightly decreases PCNA. In conclusion, PsAE is composed by phenolic compounds which demonstrate cytotoxic and antitumoral properties when is orally administrated. Presented results support future research of PsAE as a potential phytomedicine for cancer treatment.

阿根廷本土植物 Prosopis strombulifera (PsAE) 的水提物，通过对人类癌细胞系诱导细胞停滞、坏死和凋亡，展现出细胞毒性；且在克隆存活率降低的同时，未产生遗传毒性效应及口服动物毒性。迄今为止，其化学提取物组成及其在体抗肿瘤特性尚属未知；本研究的目的是探究这些特性。PsAE 通过化学指纹图谱进行了表征，其代谢组通过串联超高效液相色谱-光电二极管阵列-高分辨飞行时间质谱联用技术进行鉴定。通过二甲基肼（DMH）的注射诱导结直肠癌，通过 B16-F0 S.C. 细胞的注射诱导黑色素瘤；随后，动物通过口服给予 PsEA 治疗。为了将体内结果与体外细胞毒性相关联，培养 B16-F0 细胞以确定：通过染色排除实验、MTT 和 CFSE 稀释法测定细胞增殖和活力；通过流式细胞术测定细胞周期分布；以及通过免疫印迹分析 p21cip1、PCNA、裂解的 caspase 3、裂解的 PARP 和 TUBA1A。基于超高效液相色谱-光电二极管阵列-质谱联用技术，鉴定出二十六种化合物，包括：5 种简单有机酸、4 种酚酸、4 种缩合单宁、11 种黄酮类化合物和 2 种氧化脂类。在 C57BL6 小鼠中，PsAE 显著提高了结直肠癌的中位生存期，并减少了黑色素瘤的最终体积和重量。在培养的细胞中，治疗诱导了 p21 的过表达、通过 G2/M 细胞周期阻滞引起的细胞停滞和凋亡；而在体内黑色素瘤中，治疗上调了 p21 并轻微降低了 PCNA。总之，PsAE 由酚类化合物组成，当口服给药时，这些化合物展现出细胞毒性和抗肿瘤特性。所呈现的结果支持将 PsAE 作为一种潜在植物药用于癌症治疗的未来研究。