Baghban Arezoo, Heravi Mohammad Momen, Rezaee Seyed Abdolrahim, Tafaghodi Mohsen, Bozorgmehr Mohammadreza
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2025;28(8):1047-1056. doi: 10.22038/ijbms.2025.83900.18154.
Toxin B and isotoxin B (TB, isoTB) are major constituents of the tree. This study investigates the inhibitory effect of TB and isoTB on adult T-cell leukemia/lymphoma (ATLL), particularly on human T-lymphotropic virus type 1 protease (HTLV-1 PR). HTLV-1 protease (HTLV-1 PR) is an aspartic acid protease and a promising therapeutic target for human immunodeficiency virus (HIV) PR inhibitors.
The anticancer properties of plant components encapsulated in PLGA nanoparticles (NPs/ PLGA/TB) were evaluated by assays using different cell lines. Cancerous cell lines, including HTLV-1-infected-MT2, were treated with varying concentrations of TB and alcoholic extract, and a combined peptide was designed and expressed using recombined NPs/PLGA/TB in a human Fc gamma1 (HTLV-1 PR: hFc gamma1) against HTLV-1.
Our results show that the viability of cancer cells after NPs/ PLGA/TB treatment significantly decreased in a time- and dose-dependent manner using the MTT assay. The inhibitory effect of NPs/ PLGA/TB on the HTLV-1-infected-MT2 cell line, in the absence of recombinant peptide, was (38.98 ± 0.23) and in the presence was (16.18 ± 2.03) in 72 hr (<0.001). This indicates a double inhibitory effect in the presence of the peptide. The enzymatic effect of HTLV-1-protease on its fluorochrome substrate in the presence of TB and isoTB showed nearly complete enzyme inhibition.
These findings present a promising avenue for introducing therapeutic agents with anticancer properties to treat progressive cancers, such as viral ATLL, and inducing effective antiviral responses.
毒素B和异毒素B（TB，isoTB）是该树的主要成分。本研究调查了TB和isoTB对成人T细胞白血病/淋巴瘤（ATLL）的抑制作用，特别是对1型人类嗜T淋巴细胞病毒蛋白酶（HTLV-1 PR）的抑制作用。HTLV-1蛋白酶（HTLV-1 PR）是一种天冬氨酸蛋白酶，是人类免疫缺陷病毒（HIV）PR抑制剂很有前景的治疗靶点。
使用不同细胞系通过实验评估包裹在聚乳酸-羟基乙酸共聚物纳米颗粒（NPs/PLGA/TB）中的植物成分的抗癌特性。用不同浓度的TB和酒精提取物处理包括HTLV-1感染的MT2在内的癌细胞系，并设计并使用重组NPs/PLGA/TB在人Fcγ1（HTLV-1 PR：hFcγ1）中表达一种联合肽以对抗HTLV-1。
我们的结果表明，使用MTT实验，NPs/PLGA/TB处理后癌细胞的活力以时间和剂量依赖性方式显著降低。在没有重组肽的情况下，NPs/PLGA/TB对HTLV-1感染的MT2细胞系的抑制作用在72小时时为（38.98±0.23），在有重组肽时为（16.18±2.03）（<0.001）。这表明在有肽存在时具有双重抑制作用。在存在TB和isoTB的情况下，HTLV-1蛋白酶对其荧光底物的酶促作用显示几乎完全的酶抑制。
这些发现为引入具有抗癌特性的治疗药物来治疗进展性癌症，如病毒性ATLL，并诱导有效的抗病毒反应提供了一条有前景的途径。
