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[6]-姜烯酚 [(S)-5-羟基-1-(4-羟基-3-甲氧基苯基)-3-癸酮] 通过细胞遗传学机制对肉瘤 180 细胞的抗肿瘤作用。

Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms.

机构信息

Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil.

Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil.

出版信息

Biomed Pharmacother. 2020 Jun;126:110004. doi: 10.1016/j.biopha.2020.110004. Epub 2020 Mar 4.

Abstract

BACKGROUND

[6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice.

METHODS

The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 μM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 μM) and hydrogen peroxide (85.33 μM) were used as positive controls.

RESULTS

[6]-Gingerol, especially at concentrations of 42.66 and 85.33 μM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with HO (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress.

CONCLUSIONS

Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

摘要

背景

[6]-姜酚[(S)-5-羟基-1-(4-羟基-3-甲氧基苯基)-3-癸酮]因其具有抗氧化、止吐、抗炎和抗癌特性,被报道具有多种民族药理学用途。本研究评估了[6]-姜酚在肉瘤 180 原代细胞以及小鼠外周血淋巴细胞中的抗肿瘤作用。

方法

通过应用细胞遗传学生物标志物来评估[6]-姜酚的遗传毒性、致突变性和细胞凋亡作用。用[6]-姜酚在 21.33、42.66 和 85.33μM 浓度下处理腹水细胞,并通过台盼蓝试验和彗星试验以及细胞有丝分裂阻断微核试验进行细胞毒性测定,同时用阿霉素(6μM)和过氧化氢(85.33μM)作为阳性对照。

结果

[6]-姜酚,特别是在 42.66 和 85.33μM 浓度下,通过诱导细胞凋亡,显著降低肉瘤 180 细胞的存活率和细胞分裂率,表现出明显的细胞毒性。在所测试浓度下的遗传毒性表现为 DNA 损伤指数和频率的增加。[6]-姜酚在所有测试浓度下均未诱导明显的着丝粒外和/或断裂剂效应。然而,它确实诱导了其他核异常,如核质桥、核芽和细胞凋亡。在使用 HO(挑战试验)对肿瘤细胞和健康细胞进行共处理时观察到的遗传毒性表明,[6]-姜酚可能诱导氧化应激。

结论

观察结果表明,[6]-姜酚可能是一种有前途的抗肿瘤药物制剂候选物,因为它具有细胞毒性和与核改变(特别是通过细胞凋亡)引起的遗传不稳定性相关的机制。

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