|Table of Contents|

β-sitosterol inhibits the proliferation of K562/ADR cells and promotes apoptosis and differentiation through oxidative stress induced by ROS accumulation

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 04
Page:
641-645
Research Field:
Publishing date:

Info

Title:
β-sitosterol inhibits the proliferation of K562/ADR cells and promotes apoptosis and differentiation through oxidative stress induced by ROS accumulation
Author(s):
ZHAO Bingjie; CHE Hong; HU Lian; YI Wenjing; HOU Zhufa
Department of Hematology，Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Sichuan Chengdu 610072,China.
Keywords:
chronic myelogenous leukemia; β-sitosterol; erythrocyte differentiation; oxidative stress; in vitro
PACS:
R733.72
DOI:
10.3969/j.issn.1672-4992.2024.04.009
Abstract:
Objective:To investigate the effect of β-sitosterol on proliferation,apoptosis and differentiation of CML cell line K562/ADR and its possible mechanism.Methods:Cytotoxicity test was used to calculate the half inhibition rate concentration (IC50) of β-sitosterol on K562/ADR cells.CCK-8 method was used to detect the cell proliferation rate.Flow cytometry was used to detect the cell apoptosis rate and mitochondrial membrane potential decline rate.Spectrophotometry was used to detect the SOD activity and MDA content in cell supernatant.Fluorescence kit was used to detect the ROS intensity.The erythrocyte differentiation was detected by benzidine staining,and the protein expression levels of GATA-1,β-globin and NF-E2 were detected by Western blot.Results:The IC50 of β-sitosterol on K562/ADR cells was 163.64 μmol/L.Compared with control group,β-sitosterol at three concentrations inhibited cell proliferation,promoted cell apoptosis and erythrocyte differentiation,decreased SOD activity and mitochondrial membrane potential,increased MDA and ROS content,and increased GATA-1,β-globin and NF-E2 protein expression levels (P＜0.01).Conclusion:β-sitosterol can inhibit the proliferation of K562/ADR cells,promote cell apoptosis,and induce erythrocyte differentiation.The mechanism may be that β-sitosterol causes oxidative stress imbalance by promoting ROS accumulation.

References:

［1］ MILOJKOVIC D,LYON AR,MEHTA P,et al.Cardiovascular risk in chronic myeloid leukaemia:A multidisciplinary consensus on screening and management［J］.Eur J Haematol,2023,111(2):201-210.
［2］ TUSA I,CHELONI G,POTETI M,et al.In vitro comparison of the effects of imatinib and ponatinib on chronic myeloid leukemia progenitor/stem cell features［J］.Target Oncol,2020,15(5):659-671.
［3］ CIAFFAGLIONE V,CONSOLI V,INTAGLIATA S,et al.Novel tyrosine kinase inhibitors to target chronic myeloid leukemia［J］.Molecules,2022,27(10):3220.
［4］ HOLYOAKE TL,VETRIE D.The chronic myeloid leukemia stem cell:stemming the tide of persistence［J］.Blood,2017,129(12):1595-1606.
［5］ RADICH JP,HOCHHAUS A,MASSZI T,et al.Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia:5-year update of the ENESTfreedom trial［J］.Leukemia,2021,35(5):1344-1355.
［6］ TUSA I,CHELONI G,POTETI M,et al.Targeting the extracellular signal-regulated kinase 5 pathway to suppress human chronic myeloid leukemia stem cells［J］.Stem Cell Reports,2018,11(4):929-943.
［7］ KANTARJIAN HM,HUGHES TP,LARSON RA,et al.Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase:ENESTnd 10-year analysis［J］.Leukemia,2021,35(2):440-453.
［8］ 王信，马传江，杨培民，等.白花蛇舌草抗炎、抗肿瘤作用研究进展［J］.中国现代应用药学，2020，37(19)：2420-2427. WANG X,MA CJ,YANG PM,et al.Research progress of anti-inflammatory and anti-tumor effects of hedyotis diffusa willd ［J］.Chinese Journal of Modern Applied Pharmacy,2020,37(19):2420-2427.
［9］ 陈筱凡.白花蛇舌草提取物体外抑制K562细胞增殖实验研究［J］.浙江中西医结合杂志，2013，23(1)：14-17. CHEN XF.Hedyotis herb extracts inhibited the proliferation of human leukemia cell line K562 in vitro ［J］.Zhejiang Journal of Integrated Traditional Chinese and Western Medicine,2013,23(1):14-17.
［10］ 吴逢选，周郁鸿，叶宝东.白花蛇舌草抗肿瘤机制研究进展及其在血液病中的应用［J］.中华中医药杂志，2015，30(1)：167-169. WU FX,ZHOU YH,YE BD.Research progress on anti-tumor effect and mechanisms of hedyotis diffusa willd and its application in blood disease ［J］.China Journal of Traditional Chinese Medicine and Pharmacy,2015,30(1):167-169.
［11］ YI Z,WANG Z,LI H,et al.Inhibitory effect of tellimagrandin I on chemically induced differentiation of human leukemia K562 cells［J］.Toxicol Lett,2004,147(2):109-119.
［12］ OKABE S,GOTOH A.Effect of asciminib and vitamin K2 on Abelson tyrosine-kinase-inhibitor-resistant chronic myelogenous leukemia cells［J］.BMC Cancer,2023,23(1):827.
［13］ MINASSIAN LM,COTECHINI T,HUITEMA E,et al.Hypoxia-induced resistance to chemotherapy in cancer［J］.Adv Exp Med Biol,2019,1136:123-139.
［14］ ZHANG F,LIU Z,HE X,et al.β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund's adjuvant-induced arthritis in rats:involvement of NF-кB and HO-1/Nrf-2 pathway［J］.Drug Deliv,2020,27(1):1329-1341.
［15］ SMUKOWSKA-GORYNIA A,RZYMSKI P,MARCINKOWSKA J,et al.Prognostic value of oxidative stress markers in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension［J］.Oxid Med Cell Longev,2019,2019:3795320.
［16］ TRCK P,FRAGA S,SALVADOR I,et al.Blueberry extract decreases oxidative stress and improves functional parameters in lungs from rats with pulmonary arterial hypertension［J］.Nutrition,2020,70:110579.
［17］ 林兰明，宋征宇，胡瑾.金合欢素调节TLR4/NLRP3信号通路对脑缺血再灌注损伤模型大鼠的保护作用［J/OL］.中国中药杂志［2023-09-11］.https://kns.cnki.net/kcms/detail/11.2272.r.20230721.1722.002.html.DOI:10.19540/j.cnki.cjcmm.20230719.401. LIN LM,SONG ZY,HU J.Acacetin protects rats from cerebral ischemia-reperfusion injury by regulating TLR4/NLRP3 signaling pathway［J/OL］.China Journal of Chinese Materia Medica［2023-09-11］.https://kns.cnki.net/kcms/detail/11.2272.r.20230721.1722.002.html.DOI:10.19540/j.cnki.cjcmm.20230719.401.
［18］ 丁碧莹，王学锋.GATA结合蛋白1的造血调控功能及其突变导致的红系/巨核系相关遗传病［J］.中国输血杂志，2023，36(1)：85-90. DING BY,WANG XF.Hematopoietic regulation of transcription factor GATA1 and mutations causing hereditary erythroid and megakaryocytic disorders［J］.Chinese Journal of Blood Transfusion,2023,36(1):85-90.
［19］ ZHANG C,GUO LY,MU D,et al.Induction of apoptosis and erythroid differentiation of human chronic myelogenous leukemia K562 cells by low concentrations of lidamycin［J］.Oncol Rep,2019,41(1):475-482.

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