标准化植物制剂和来自 Ibervillea sonorae (S. Watson) greene 的葫芦素 IIb 通过抑制 Nrf2 诱导宫颈癌细胞凋亡。
Standardized phytopreparations and cucurbitacin IIb from Ibervillea sonorae (S. Watson) greene induce apoptosis in cervical cancer cells by Nrf2 inhibition.
机构信息
Departamento de Ciencias Químico Biológicas y de la Salud, Universidad de Sonora - Blvd. Luis Donaldo Colosio esq. Rosales S/N, Centro, Hermosillo Sonora, CP: 83000, Mexico; Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Rodovia Araraquara - Jaú, Km 1, Araraquara, São Paulo, CEP: 14800-903, Brazil.
Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora - Avenida Universidad e Irigoyen, Caborca Sonora, CP:83621, Mexico.
出版信息
J Ethnopharmacol. 2022 Nov 15;298:115606. doi: 10.1016/j.jep.2022.115606. Epub 2022 Aug 6.
ETHNOPHARMACOLOGY RELEVANCE
Ibervillea sonorae (S. Watson) Greene is a plant from northwestern Mexico, known as "Wereke" or "Guareque", used by the Mayo ethnic group to treat diabetes and cancer. Cucurbitacin IIb (CIIb), isolated from I. sonorae has apoptotic and antitumor activity in a model of cervical cancer with the HeLa cell line. One pathway affected by cucurbitacins is Nrf2, a glutathione transferase (GST) transcription factor, important in the regulation of mitochondrial oxidative stress (MOS). A signal of MOS is the change in the mitochondrial membrane potential (ΔΨm), which has been detected in HeLa in the presence of CIIb. Fito-Ison-EtOH (Etanison) and Fito-Ison-EtOAc (Acetison) are phytopreparations from I. sonorae standardized according to their CIIb content (6.7 mg/g and 18.4 mg/g of CIIb, respectively). Etanison and Acetison have been reported to induce morphological changes in HeLa like those induced by CIIb.
AIM OF THE STUDY
To evaluate the apoptotic and Nrf2 inhibition activity of the phytopreparations Acetison and Etanison from Ibervillea Sonorae in the HeLa cervical cancer cell line.
MATERIALS AND METHODS
Antiproliferative activity was evaluated by the MTT method at 24, 48, and 72 h. For Acetison and Etanison, serial concentrations from 6.25 μg/mL to 100 μg/mL were tested, and for CIIb from 1.56 μg/mL to 50 μg/mL. The expression of Nrf2, caspase 3, and caspase 9 was evaluated by western blot, using concentrations of 30 μg/mL for Acetison, 50 μg/mL for Etanison, and 15 μg/mL for CIIb. Cisplatin was used as a positive control.
RESULTS AND CONCLUSIONS
Apoptotic activity of Etanison and Acetison was demonstrated in HeLa, due to the presence of caspase-9 and caspase-3 in western blot assays. Likewise, both the phytopreparations and CIIb showed inhibition of Nrf2, associating apoptotic activity with the inhibition of the GST transcription factor. In this sense, the phytopreparations of I. sonorae, as well as their derivatives, have the potential to obtain and develop anticancer products.
民族药理学相关性
索诺拉仙人掌（S. 沃森）格林是一种来自墨西哥西北部的植物，被称为“Wereke”或“Guareque”，被马约族用于治疗糖尿病和癌症。从索诺拉仙人掌中分离出的葫芦素 IIb（CIIb）在宫颈癌 HeLa 细胞系模型中具有凋亡和抗肿瘤活性。受葫芦素影响的途径之一是 Nrf2，一种谷胱甘肽转移酶（GST）转录因子，在调节线粒体氧化应激（MOS）中很重要。MOS 的一个信号是线粒体膜电位（ΔΨm）的变化，在 CIIb 存在的情况下，已经在 HeLa 中检测到了这种变化。Fito-Ison-EtOH（Etanison）和 Fito-Ison-EtOAc（Acetison）是根据其 CIIb 含量（分别为 6.7mg/g 和 18.4mg/g 的 CIIb）标准化的索诺拉仙人掌植物制剂。据报道，Etanison 和 Acetison 可诱导 HeLa 细胞发生类似于 CIIb 诱导的形态变化。
研究目的
评估来自 Ibervillea Sonorae 的植物制剂 Acetison 和 Etanison 在宫颈癌 HeLa 细胞系中的凋亡和 Nrf2 抑制活性。
材料和方法
通过 MTT 法在 24、48 和 72 小时评估抗增殖活性。对于 Acetison 和 Etanison，测试了从 6.25μg/mL 到 100μg/mL 的系列浓度，而对于 CIIb，则测试了从 1.56μg/mL 到 50μg/mL 的系列浓度。使用浓度为 30μg/mL 的 Acetison、50μg/mL 的 Etanison 和 15μg/mL 的 CIIb 进行 Western blot 评估 Nrf2、caspase 3 和 caspase 9 的表达。顺铂被用作阳性对照。
结果和结论
由于 Western blot 检测到 caspase-9 和 caspase-3 的存在，Etanison 和 Acetison 在 HeLa 中表现出凋亡活性。同样，植物制剂和 CIIb 均显示出对 Nrf2 的抑制作用，将凋亡活性与 GST 转录因子的抑制联系起来。从这个意义上说，I. sonorae 的植物制剂及其衍生物有可能获得和开发抗癌产品。
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