Anticancer potential of nerolidol on acute lymphoblastic leukemia cells through the interactions with the NF-κB/STAT-3 and PI3K/Akt signaling pathways.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Xuejiao Wang, Ke Wang, Hengfei Du
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引用次数: 0

Abstract

Background: Leukemia may form at any age, from newborns to the elderly, and accounts for considerable mortality worldwide.

Objectives: Nerolidol (NRD) is isolated from the aromatic florae oils and was found to have anticancer activities. However, the role of NRD in antiproliferative and apoptosis actions in acute lymphoblastic leukemia (ALL) is unclear.

Material and methods: Human ALL cell lines, MOLT-4, were used to examine the potential anticancer mechanisms of NRD on cellular proliferation, reactive oxygen species (ROS)-mediated apoptosis, oxidative stress markers, caspases, PI3K/AKT, nuclear factor kappa B (NF-κB), and STAT-3/VEGF/Bcl-2 signaling pathways.

Results: The MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay demonstrated that NRD inhibited MOLT-4 cell proliferation in a concentration-dependent manner, with an IC50 value of 30 μM. It was found that NRD (20 and 30 μM/mL) resulted in accumulated intracellular ROS, reduced oxidative stress and loss of mitochondrial membrane potential (MMP) in MOLT-4 cells in a concentration-related way. Nerolidol was able to induce apoptosis, as evidenced by dual acridine orange/ethidium bromide (AO/EB) staining. The levels of antioxidants, caspases-3, -8 and -9 were enhanced by NRD. This research proves that NRD instantaneously triggers ROS-mediated pro-apoptotic signaling and caspases and attenuates PI3K/Akt/NF-κB and STAT3/VEGF/Bcl-2 anti-apoptotic signaling.

Conclusions: Our results suggest that NRD treatment stimulates apoptosis in MOLT-4 cells by causing the accumulation of intracellular ROS through PI3K/AKT/STAT-3 signaling pathways.

神经树醇通过与NF-κB/STAT-3和PI3K/Akt信号通路相互作用对急性淋巴细胞白血病细胞的抗癌潜力
背景:白血病可在任何年龄形成,从新生儿到老年人,在世界范围内造成相当大的死亡率。目的:从植物精油中分离得到橙花醇(NRD),发现其具有抗癌活性。然而,NRD在急性淋巴细胞白血病(ALL)中的抗增殖和凋亡作用尚不清楚。材料和方法:采用人ALL细胞系MOLT-4,研究NRD对细胞增殖、活性氧(ROS)介导的细胞凋亡、氧化应激标志物、半胱天冬酶、PI3K/AKT、核因子κB (NF-κB)和STAT-3/VEGF/Bcl-2信号通路的潜在抗癌机制。结果:MTT(3-(4,5 -二甲基噻唑-2)- 2,5 -二苯基溴化四唑)实验表明,NRD抑制MOLT-4细胞增殖呈浓度依赖性,IC50值为30 μM。结果发现,NRD (20 μM/mL和30 μM/mL)使MOLT-4细胞细胞内ROS积累,氧化应激降低,线粒体膜电位(MMP)损失呈浓度相关。双吖啶橙/溴化乙啶(AO/EB)染色证实,橙花醇能诱导细胞凋亡。NRD可提高抗氧化剂caspase -3、-8和-9的水平。本研究证明NRD可瞬间触发ros介导的促凋亡信号和caspase,并减弱PI3K/Akt/NF-κB和STAT3/VEGF/Bcl-2抗凋亡信号。结论:我们的研究结果表明,NRD处理通过PI3K/AKT/STAT-3信号通路引起细胞内ROS的积累,从而刺激MOLT-4细胞凋亡。
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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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