División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, 44340, Jalisco, México.
Posgrado en Ciencias Biomédicas Orientación en Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, 44340, Jalico, México.
Fundam Clin Pharmacol. 2020 Dec;34(6):671-686. doi: 10.1111/fcp.12559. Epub 2020 May 11.
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.
乳腺癌是全球女性最常见的癌症，所有乳腺癌类型都普遍存在耐药性。将天然产物与化疗药物联合使用引起了关注，因为发现天然化合物可以增强标准癌症化疗药物的疗效并防止副作用。在不同的天然产物中，大蒜因其抗肿瘤特性而受到认可。据认为，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细胞死亡、衰老及其在腔 A 和三阴性乳腺癌细胞中的衰老溶解作用的影响。MCF-7（腔 A）和 HCC-70（三阴性）细胞进行培养并分别用不同浓度的蒜氨酸或蒜素处理。然后，使用 WST-1 试剂测定细胞活力。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 评估凋亡相关基因。使用溴脱氧尿苷掺入法测量增殖。我们还评估了克隆形成、衰老（β-半乳糖苷酶染色）以及化合物的衰老溶解作用。我们的结果表明，蒜素具有抗增殖、抗集落形成和衰老溶解作用。此外，蒜素通过丧失 ΔΨm、激活 caspase-3、caspase-8 和 caspase-9、上调 NOXA、P21 和 BAK 以及下调 BCL-XL 表达，降低细胞活力并诱导细胞凋亡。与蒜素相反，蒜氨酸促进了乳腺癌细胞的集落形成，诱导了衰老，但没有表现出促凋亡作用。
