Anti-Cancer Role of Dendrosomal Nano Solanine in Chronic Myelogenous Leukemia Cell Line through Attenuation of PI3K/AKT/mTOR Signaling Pathway and Inhibition of hTERT Expression.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-03-27 DOI:10.2174/1874467215666220516143155

Golareh Asgaritarghi, Seyedeh Sahar Mortazavi Farsani, Dina Sadeghizadeh, Farhood Najaﬁ, Majid Sadeghizadeh

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引用次数: 2

Abstract

Background: Solanine was primarily known as a toxic compound. Nonetheless, recently the apoptotic role of solanine through suppression of PI3K/AKT/mTOR signaling pathway has been shown against many malignancies except chronic myelogenous leukemia (CML). Sustaining the aforementioned pro-survival pathway, BCR-ABL fused oncoprotein in CML activates NF-kB and c- MYC for apparent immortalizing factor hTERT. Since solanine is a poor water-soluble molecule, herein, a nanocarrier was employed to intensify its pernicious effect on cancerous cells.

Objective: The current research aimed at evaluating the effect of dendrosomal nano solanine (DNS) on leukemic and HUVEC cells.

Methods: DNS characterization was determined by NMR, DLS and TEM. The viability, apoptosis and cell cycle of DNS and imatinib-treated cells were determined. A quantitative real-time PCR was employed to measure the expression of PI3K, AKT, mTOR, S6K, NF-kB, c-MYC and hTERT mRNAs. The Protein levels were evaluated by western blot.

Results: Investigating the anticancer property of free and dendrosomal nano solanine (DNS) and the feasible interplaying between DNS and imatinib on leukemic cells, we figured out the potential inhibitory role of DNS and DNS+IM on cancerous cells in comparison with chemotherapy drugs. Moreover, results revealed that the encapsulated form of solanine was much more preventive on the expression of PI3KCA, mTOR, NF-kB, c-MYC and hTERT accompanied by the dephosphorelating AKT protein.

Conclusion: The results advocate the hypothesis that DNS, rather than solanine, probably due to impressive penetration, can restrain the principal pro-survival signaling pathway in erythroleukemia K562 and the HL60 cell lines and subsequently declined mRNA level of hTERT which causes drug resistance during long-term treatment. Additionally, combinational treatment of DNS and IM could also bestow an additive anti-leukemic effect. As further clinical studies are necessary to validate DNS efficacy on CML patients, DNS could have the potency to be considered as a new therapeutic agent even in combination with IM.

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树状体纳米茄碱通过抑制PI3K/AKT/mTOR信号通路和抑制hTERT表达在慢性髓性白血病细胞中的抗癌作用

背景:龙葵碱最初被认为是一种有毒化合物。尽管如此，近年来，龙葵碱通过抑制PI3K/AKT/mTOR信号通路的凋亡作用已被证明可用于除慢性髓性白血病(CML)外的许多恶性肿瘤。维持上述促生存途径，CML中BCR-ABL融合癌蛋白激活NF-kB和c- MYC的表观永生化因子hTERT。由于龙葵碱是一种水溶性较差的分子，因此本文采用纳米载体来增强其对癌细胞的有害作用。目的:研究树状体纳米龙葵碱(DNS)对白血病和HUVEC细胞的作用。方法:采用NMR、DLS、TEM对其进行表征。测定DNS处理细胞和伊马替尼处理细胞的活力、凋亡和细胞周期。采用实时荧光定量PCR检测PI3K、AKT、mTOR、S6K、NF-kB、c-MYC和hTERT mrna的表达。western blot检测蛋白水平。结果:通过研究游离纳米茄碱(DNS)和树状体纳米茄碱(DNS)的抗癌特性，以及DNS与伊马替尼对白血病细胞的可能相互作用，发现了与化疗药物相比，DNS和DNS+IM对癌细胞的潜在抑制作用。此外，结果显示，茄碱包封形式对PI3KCA、mTOR、NF-kB、c-MYC和hTERT的表达具有更强的预防作用，并伴有去磷相关AKT蛋白的表达。结论:这些结果支持这样的假设:DNS而非茄碱，可能是由于其渗透力强，抑制了红细胞白血病K562和HL60细胞系中主要的促生存信号通路，从而降低了hTERT mRNA水平，从而导致长期治疗期间的耐药。此外，DNS和IM联合治疗也可给予附加的抗白血病作用。由于需要进一步的临床研究来验证DNS对CML患者的疗效，因此即使与IM联合使用，DNS也有可能被认为是一种新的治疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.