Martínez-Castillo Macario, Villegas-Sepúlveda Nicolas, Meraz-Rios Marco A, Hernández-Zavala Araceli, Berumen Jaime, Coleman Mathew A, Orozco Lorena, Cordova Emilio J
Department of Molecular Biomedicine, Center of Studies and Advance Research, 07360 Mexico City, Mexico.
Section of Research and Postgraduate, Superior School of Medicine, National Institute Polytechnique, Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomás, 11350 Mexico City, Mexico.
Oncol Lett. 2018 May;15(5):6777-6783. doi: 10.3892/ol.2018.8112. Epub 2018 Feb 23.
Curcumin is a phytochemical with potent anti-neoplastic properties. The antitumoral effects of curcumin in cells derived from chronic or acute myeloid leukemia have been already described. However, a comparative study of the cytostatic and cytotoxic effects of curcumin on chronic and acute myeloid leukemia cells has not yet been performed. In the present study, the cellular effects of curcumin on cell lines derived from chronic or acute myeloid leukemia were examined. Dose and time-response assays were performed with curcumin on HL-60 and K562 cells. Cell viability was evaluated with trypan blue exclusion test and cell death by flow cytometry using a fluorescent molecular probe. A cell cycle profile was analyzed, and protein markers of cell cycle progression and cell death were investigated. In the present study, the K562 cells showed a higher sensitivity to the cytostatic and cytotoxic effects of curcumin compared with HL-60. In addition, curcumin induced G1 phase arrest in HL-60 cells and G2/M phase arrest in K562 cells. Furthermore, curcumin-related cell death in HL-60 was associated with the processed forms of caspases-9 and -3 proteins, whereas in K562 cells, both the processed and the unprocessed forms were present. Accordingly, activity of these caspases was significantly higher in HL-60 cells compared with that in K562. In conclusion, curcumin elicits different cellular mechanisms in chronic or acute myeloid leukemia cells and the powerful antitumoral effect was more potent in K562 compared with HL-60 cells.
姜黄素是一种具有强大抗肿瘤特性的植物化学物质。姜黄素对慢性或急性髓系白血病来源细胞的抗肿瘤作用已有相关描述。然而，尚未对姜黄素对慢性和急性髓系白血病细胞的细胞生长抑制和细胞毒性作用进行比较研究。在本研究中，检测了姜黄素对慢性或急性髓系白血病来源细胞系的细胞作用。用姜黄素对HL - 60和K562细胞进行剂量和时间反应测定。通过台盼蓝排斥试验评估细胞活力，并使用荧光分子探针通过流式细胞术检测细胞死亡情况。分析细胞周期图谱，并研究细胞周期进程和细胞死亡的蛋白质标志物。在本研究中，与HL - 60相比，K562细胞对姜黄素的细胞生长抑制和细胞毒性作用表现出更高的敏感性。此外，姜黄素诱导HL - 60细胞G1期阻滞和K562细胞G2/M期阻滞。此外，HL - 60细胞中与姜黄素相关的细胞死亡与半胱天冬酶 - 9和 - 3蛋白的加工形式有关，而在K562细胞中，加工形式和未加工形式均存在。因此，与K562细胞相比，这些半胱天冬酶在HL - 60细胞中的活性显著更高。总之，姜黄素在慢性或急性髓系白血病细胞中引发不同的细胞机制，与HL - 60细胞相比，K562细胞中强大的抗肿瘤作用更显著。
