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Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple-negative breast cancer: Caspase, ΔΨm, and pro-apoptotic gene involvement.
Fundamental & Clinical Pharmacology ( IF 2.1 ) Pub Date : 2020-04-14 , DOI: 10.1111/fcp.12559
Vida Celeste Rosas-González 1, 2 , Martha Cecilia Téllez-Bañuelos 3 , Georgina Hernández-Flores 1 , Alejandro Bravo-Cuellar 1, 4 , Adriana Aguilar-Lemarroy 1 , Luis Felipe Jave-Suárez 1 , Jesse Haramati 3 , Fabiola Solorzano-Ibarra 2 , Pablo Cesar Ortiz-Lazareno 1
Affiliation  

Breast cancer is the most frequent cancer in women worldwide, and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo‐sulfur compounds, especially alliin and allicin. Here, we evaluated the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple‐negative breast cancer cells. MCF‐7 (luminal A) and HCC‐70 (triple‐negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST‐1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC‐10 fluorometric assay kit. Apoptosis‐related genes were evaluated by RT‐PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (β‐Galactosidase Staining), and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspase‐3, caspase‐8, and caspase‐9 activation, upregulation of NOXA, P21, and BAK, as well as downregulation of BCL‐XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence, and did not exhibit pro‐apoptotic effects in breast cancer cells.

中文翻译:

大蒜素和大蒜素对管腔A和三阴性乳腺癌的凋亡和衰老的不同作用:Caspase,ΔΨm和促凋亡基因参与。

乳腺癌是全世界女性中最常见的癌症,并且耐药性在所有乳腺癌类型中都很常见。天然产物与化学疗法的结合引起了人们的注意,因为发现天然化合物增强了标准癌症化学疗法药物的作用并防止副作用。对于不同的天然产品,大蒜因其抗肿瘤特性而闻名。建议其抗癌作用与其有机硫化合物有关,尤其是蒜氨酸和蒜素。在这里,我们评估了这两种分子对腔A和三阴性乳腺癌细胞的细胞死亡,衰老及其衰老的影响。培养MCF-7(腔A)和HCC-70(三阴性)细胞,并用不同浓度的大蒜素或大蒜素处理。然后,使用WST-1试剂确定细胞活力。通过流式细胞术评估细胞凋亡和半胱天冬酶活性。使用JC-10荧光测定试剂盒评估ΔΨm。通过RT-PCR评估与凋亡相关的基因。使用溴脱氧尿苷掺入测量增殖。我们还评估了这些化合物的克隆形成性,衰老(β-半乳糖苷酶染色)和衰老作用。我们的研究结果表明,大蒜素具有抗增殖,抗龋齿和抗衰老作用。此外,大蒜素会降低ΔΨm,caspase-3,caspase-8和caspase-9的活化,NOXA,P21和BAK的上调以及BCL-XL的表达下调,从而降低细胞活力并诱导凋亡。与大蒜素相反,大蒜素能促进克隆形成,诱导衰老,并且在乳腺癌细胞中不显示促凋亡作用。
更新日期:2020-04-14
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