García-Morales Lázaro, Ríos-Castro Emmanuel, Ramírez José Tapia, Meza Isaura
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico.
Unidad de Genómica, Proteómica y Metabolómica (UGPM), Laboratorio Nacional de Servicios Experimentales (LaNSE), Centro de Investigación y de Estudios Avanzados, Avenida Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico.
Int J Mol Sci. 2025 May 15;26(10):4721. doi: 10.3390/ijms26104721.
Cannabidiol (CBD) has shown promise in treating cancers with an inflammatory microenvironment. Although it has been demonstrated that IL-1β induces epithelial-mesenchymal transition (EMT) of MCF-7 cells and CBD reverts this process, in restoring the epithelial non-invasive phenotype, there is limited understanding of how this cannabinoid regulates these processes. In this work, MCF-7 cells were induced to adopt an aggressive phenotype (6D cells), which was reversed by CBD. Then, protein expression was analyzed by mass spectrometry to compare 6D vs. MCF-7 cells and 6D+CBD vs. 6D cells proteomes. Novel proteins associated with EMT and CBD signaling were identified. Twenty-four of them were oppositely regulated by IL-1β and CBD, suggesting new points of crosstalk between the IL-1β and CBD signaling pathways. From the data, two protein networks were constructed: one related to EMT with 58 up-regulated proteins and another with 21 related to CBD signaling. The first one showed the proteins BRCA1, MSN, and CORO1A as the key axis that contributes to the establishment of a mesenchymal phenotype. In the CBD signaling, the key axis was formed by SUPT16H, SETD2, and H2BC12, which suggests epigenetic regulation by CBD in the restoration of an epithelial phenotype of breast cancer cells, providing new targets for anticancer therapy.
大麻二酚（CBD）在治疗具有炎症微环境的癌症方面已显示出前景。尽管已经证明白细胞介素-1β（IL-1β）可诱导MCF-7细胞发生上皮-间质转化（EMT），且CBD可逆转这一过程，在恢复上皮非侵袭性表型方面，但对于这种大麻素如何调节这些过程的了解有限。在这项研究中，MCF-7细胞被诱导呈现侵袭性表型（6D细胞），而CBD可使其逆转。然后，通过质谱分析蛋白质表达，以比较6D细胞与MCF-7细胞以及6D + CBD细胞与6D细胞的蛋白质组。鉴定出了与EMT和CBD信号传导相关的新蛋白质。其中24种受IL-1β和CBD的反向调节，提示IL-1β和CBD信号通路之间存在新的串扰点。根据这些数据，构建了两个蛋白质网络：一个与EMT相关，有58种上调蛋白质，另一个与CBD信号传导相关，有21种。第一个网络显示蛋白质BRCA1、MSN和CORO1A是促成间充质表型建立的关键轴。在CBD信号传导中，关键轴由SUPT16H、SETD2和H2BC12组成，这表明CBD在恢复乳腺癌细胞上皮表型过程中存在表观遗传调控，为抗癌治疗提供了新靶点。
