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Tabebuia chrysantha 的茎提取物通过靶向 Ehrlich 腹水癌细胞中的 sEGFR 诱导细胞凋亡。

Stem extract of Tabebuia chrysantha induces apoptosis by targeting sEGFR in Ehrlich Ascites Carcinoma.

机构信息

Pharmacology Research Division, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, India.

Pharmaceutical Analysis Research Laboratory, CMR College of Pharmacy, Hyderabad, Telangana, India.

出版信息

J Ethnopharmacol. 2019 May 10;235:219-226. doi: 10.1016/j.jep.2019.02.023. Epub 2019 Feb 12.

DOI:10.1016/j.jep.2019.02.023
PMID:30769041
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The plant Tabebuia chrysantha (Jaq.) Nicholson (Bignoniaceae) is commonly known as "Golden Goddess" in the Southern part of India and "Golden Trumpet Tree " in Central America. Stems of this plant have been traditionally used for antioxidant, anti-inflammatory, antimicrobial and anticancer actions.

AIM OF THE STUDY

To evaluate the antitumor activity of methanol extract of Tabebuia chrysantha stem (METC).

MATERIALS AND METHODS

The in vivo antitumor potential of METC against Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters, biochemical parameters, and antioxidant parameters. The in vitro antitumor potential of METC at different concentrations (100, 200, 400, 800, 1000) µg/mL has been evaluated, by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and Trypan blue dilution assay for a period of 3 h treatment. Before that, the crude extract was pre-screened for cytotoxicity property using Brine shrimp lethality bioassay.

RESULTS

Phytoconstituents 2-Hydroxynaphthalene-1,4-dione, β-lapachone and 2-((dimethylamino)methyl)-3-methoxynaphthalene-1,4-dione were isolated from the METC. Their occurrence and structures were determined by HPLC chromatography, UV spectroscopy, and 1D and D NMR spectroscopies respectively. The extract showed a direct cytotoxic effect on EAC cells in a dose-dependent manner with IG value 463.27 µg/mL in MTT assay and 443.58 µg/mL in trypan blue dilution assay. The METC (300 mg/kg) and 5-FU (30 mg/kg) exhibited significant (p < 0.001) decrease in tumor volume, tumor weight and viable cell count of EAC-treated mice. Also, hematological profile, tissue parameters such as lipid peroxidation, reduced glutathione, superoxide dismutase, and catalase were reverted to the normal levels compared to the EAC control group. The Western blotting analysis demonstrated apoptosis of carcinoma was due to inhibition of soluble epidermal growth factor receptor proteins (sEGFR) expression in the blood.

CONCLUSION

The antitumor potential of the stem extract of T chrysantha was due to naphthaquinones and polyphenol content in the crude extract and so T chrysantha could be a cytotoxic plant to control tumor growth.

摘要

植物学相关性

在印度南部,Tabebuia chrysantha(Jaq.)Nicholson(紫葳科)俗称“金女神”,在中美洲则被称为“金喇叭树”。该植物的茎传统上用于抗氧化、抗炎、抗菌和抗癌作用。

研究目的

评估甲醇提取物 Tabebuia chrysantha 茎(METC)的抗肿瘤活性。

材料和方法

通过评估肿瘤体积、活和死肿瘤细胞计数、肿瘤重量、血液学参数、生化参数和抗氧化参数,评估 METC 对瑞士白化病小鼠艾氏腹水癌(EAC)的体内抗肿瘤潜力。METC 在不同浓度(100、200、400、800、1000 µg/mL)下的体外抗肿瘤潜力通过 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物]和台盼蓝稀释测定法进行评估,为期 3 小时处理。在此之前,使用盐水虾致死生物测定法对粗提取物进行细胞毒性预先筛选。

结果

从 METC 中分离出 2-羟基萘-1,4-二酮、β-拉帕酮和 2-((二甲氨基)甲基)-3-甲氧基萘-1,4-二酮。它们的存在和结构分别通过 HPLC 色谱、UV 光谱和 1D 和 D NMR 光谱确定。提取物对 EAC 细胞具有直接的细胞毒性作用,呈剂量依赖性,MTT 测定的 IG 值为 463.27 µg/mL,台盼蓝稀释测定的 IG 值为 443.58 µg/mL。METC(300 mg/kg)和 5-FU(30 mg/kg)可显著(p < 0.001)降低 EAC 处理小鼠的肿瘤体积、肿瘤重量和活细胞计数。此外,与 EAC 对照组相比,血液学参数、脂质过氧化、还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶等组织参数均恢复正常水平。Western blot 分析表明,由于血液中可溶性表皮生长因子受体蛋白(sEGFR)表达的抑制,癌发生了凋亡。

结论

T chrysantha 茎提取物的抗肿瘤潜力归因于粗提取物中的萘醌和多酚含量,因此 T chrysantha 可能是一种控制肿瘤生长的细胞毒性植物。

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