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首页> 外文期刊>Oxidative Medicine and Cellular Longevity >Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms
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Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms

机译:Senna Velutina Roots的乙醇提取物:化学成分,体外和体内抗肿瘤效应,B16F10-NEX2黑色素瘤细胞死亡机制

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摘要

Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.
机译:皮肤黑素瘤是最具侵略性的癌症类型,其发生率每年都会增加。对黑色素瘤的目前药理治疗并不完全有效,需要鉴定新药。作为替代方案,植物衍生的天然化合物被描述为新的抗癌药物的有前途的来源。在这种情况下,本研究的目的是鉴定Senna Velutina Roots(ESVR)的乙醇提取物的化学成分,以评估其对黑色素瘤细胞的体外和体内抗肿瘤作用,并表征其作用机制。出于这些目的,通过偶联至高分辨率质谱法鉴定化学成分。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴铵(MTT)测定并基于凋亡细胞计数,在B16F10-NEX2黑色素瘤细胞系中评估提取物的体外活性。 ; DNA碎片; Necrostatin-1抑制;细胞内钙,泛肠溶酶和Caspase-3活化;反应性氧(ROS)水平;和细胞周期逮捕。在C57BL / 6小鼠的肿瘤体积进展和肺结核模型中评估提取物的体内活性。化学成分结果表明,ESVR含有儿茶素,蒽醌和PICEatannol基团的类黄酮衍生物。提取物降低了B16F10-NEX2细胞活力并促进了凋亡细胞死亡以及Caspase-3激活,随着细胞内钙和ROS水平以及亚g0 / g1相的细胞周期停留。体内,ESVR处理小鼠的肿瘤体积进展和肺转移减少了50%以上。结合,这些结果表明,ESVR在体外和体内抗肿瘤效应中,主要是细胞凋亡,从而证明其作为治疗黑素瘤和其他类型癌症的治疗剂的潜力。

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