Soltani Amin, Pourgheysari Batoul, Shirzad Hedayatollah, Sourani Zahra
Department of Immunology, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Indian J Hematol Blood Transfus. 2017 Dec;33(4):516-524. doi: 10.1007/s12288-016-0758-8. Epub 2016 Dec 8.
Acute lymphoblastic leukemia is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for about 80% of all cases of childhood leukemia. Side effects of available treatment are still main concern. Thymoquinone (TQ), a natural compound isolated from , induces growth inhibition and apoptosis in several cancer cell lines. The aim of the present study was to investigate the effect of TQ alone and in combination with doxorubicine on the proliferation inhibition and apoptosis induction of TQ in a lymphoblastic leukemia cell line. Jurkat cell line was cultured in standard condition and with concentrations of TQ (0-30 μm) and doxorubicine for 24, 48 and 72 h. Cell viability was measured by MTS assay. Apoptosis induction by TQ was assessed by annexin V-FITC/PI and flow cytometry analysis. TQ and DOX decreased cell viability with a time and dose dependent manner. The IC50 values were 19.461 ± 1.141, 17.342 ± 1.949 and 14.123 ± 1.874 μM in 24, 48 and 72 h, respectively for TQ. IC50 values for DOX were. 075 ± .0124, .028 ± .007 and.007 ± .001 μM in 24, 48 and 72 h, respectively. The level of cell apoptosis in all used concentrations of TQ (4, 8, 12, 16 and 20 μm) was higher than control group (10.2, 14.1, 36.6, 87.5 and 93.3% respectively after 24 h; 10.7, 13.9, 64.6, 92.2 and 93.1 respectively after 48 h; 2.83, 5.83, 41.4, 71.6 and 86.6% respectively after 72 h) and reached to a significant level at 12, 16 and 20 μm concentration for 24 and 48 h and 16 and 20 μm for 72 h incubation. Combination of doxorubicine and TQ lead to a synergistic cytotoxicity as compared to any of them alone. The study indicated that TQ is effective on proliferation inhibition and is a strong apoptotic inducer in Jurkat lymphoblastic cell line and has synergistic effect in combination with DOX. This combination strategy can be an alternative way for more powerful anticancer effects. Therefore, the study of the mechanism of apoptosis induction of TQ can be a step forward to in target therapy which might be considered in the future studies.
急性淋巴细胞白血病是淋巴细胞在分化早期的恶性增殖之一，约占儿童白血病病例的80%。现有治疗的副作用仍是主要关注点。从[具体植物名称缺失]中分离出的天然化合物百里醌（TQ）可诱导多种癌细胞系生长抑制和凋亡。本研究的目的是探究TQ单独及与阿霉素联合对淋巴细胞白血病细胞系增殖抑制和凋亡诱导的影响。将Jurkat细胞系在标准条件下培养，分别加入浓度为0至30 μM的TQ和阿霉素，培养24、48和72小时。通过MTS法测定细胞活力。通过膜联蛋白V-异硫氰酸荧光素/碘化丙啶和流式细胞术分析评估TQ诱导的凋亡。TQ和阿霉素以时间和剂量依赖性方式降低细胞活力。TQ在24、48和72小时的IC50值分别为19.461±1.141、17.342±1.949和14.123±1.874 μM。阿霉素在24、48和72小时的IC50值分别为0.075±0.0124、0.028±0.007和0.007±0.001 μM。所有使用浓度的TQ（4、8、12、16和20 μM）诱导的细胞凋亡水平均高于对照组（24小时后分别为10.2%、14.1%、36.6%、87.5%和93.3%；48小时后分别为10.7%、13.9%、64.6%、92.2%和93.1%；72小时后分别为2.83%、5.83%、41.4%、71.6%和86.6%），且在24和48小时时，12、16和20 μM浓度以及72小时时16和20 μM浓度达到显著水平。与单独使用任何一种药物相比，阿霉素和TQ联合导致协同细胞毒性。该研究表明，TQ对Jurkat淋巴细胞系的增殖抑制有效，是一种强大的凋亡诱导剂，且与阿霉素联合具有协同作用。这种联合策略可能是实现更强抗癌效果的另一种途径。因此研究TQ诱导凋亡的机制可能是靶向治疗向前迈进的一步，有望在未来研究中得到考虑。
