l-香叶醇通过抑制FAK的激活来减少乳腺癌细胞的粘附、迁移和侵袭。
l-carvone decreases breast cancer cells adhesion, migration, and invasion by suppressing FAK activation.
发表日期:2023 Apr 12
作者:
Lucas Trevisan França de Lima, Fernando Augusto de Oliveira Ganzella, Gabriela Casani Cardoso, Verônica Dos Santos Pires, Andressa Chequin, Giulia Luiza Santos, Karin Braun-Prado, Claudia Martins Galindo, Odair Braz Junior, Marcelo Beltrão Molento, Alexandra Acco, Eliana Rezende Adami, Erico Tosoni Costa, Célia Regina Cavichiolo Franco, Giseli Klassen, Edneia Amancio de Souza Ramos
来源:
CHEMICO-BIOLOGICAL INTERACTIONS
摘要:
乳腺癌是世界上最常见的癌症之一,现有的治疗策略存在严重的缺陷。l-香芹酮(CRV)是一种在 Mentha spicata(留兰香)中发现的单萜,已报告具有强效的抗炎作用。在这里,我们研究了 CRV 在 vitro 中对乳腺癌细胞黏附、迁移和侵袭的作用,以及该成分如何抑制携带 Ehrlich 癌瘤的小鼠的生长。在 vivo 中,CRV 的治疗显著减少了肿瘤的生长,增加了肿瘤坏死面积,并减少了携带 Ehrlich 癌瘤的小鼠中 VEGF 和 HIF-1α 的表达。此外,CRV 的抗癌效果类似于目前使用的化疗(甲氨蝶呤),而 CRV 与 MTX 的联合使用增强了化疗效果。进一步的 in vitro 机制研究显示,CRV 通过破坏点聚焦粘附调节乳腺癌细胞与细胞外基质(ECM)的相互作用,这在扫描电子显微镜(SEM)和免疫荧光等技术中得到了证明。此外,CRV 导致 β1整合素表达减少,并抑制点聚焦激酶(FAK)的激活。FAK 是几个转移过程中最重要的下游激活剂之一,包括 MMP-2介导的侵袭和 HIF-1α/VEGF血管生成刺激。这两种过程都在暴露于 CRV 的 MDA-MB-231 细胞中得到了减少。我们的结果提供了新的深入认识,关于使用 CRV 靶向 β1整合素/ FAK 信号通路,这可能是乳腺癌治疗的一个新潜在药物。版权所有 © 2023 Elsevier B.V. 发布。
Breast cancer is one of the most common types of cancer in the world and current therapeutic strategies present severe drawbacks. l-carvone (CRV), a monoterpene found in Mentha spicata (spearmint), has been reported to have potent anti-inflammatory activity. Here, we examined the role of CRV in breast cancer cell adhesion, migration and invasion in vitro and how this component could suppress the growth of Ehrlich carcinoma-bearing mice. In vivo, treatment with CRV significantly decreased tumor growth, increased tumor necrosis area, and reduced the expression of VEGF and HIF-1α in Ehrlich carcinoma-bearing mice. Furthermore, the anticancer efficacy of CRV was similar to currently used chemotherapy (Methotrexate), and the combination of CRV with MTX potentiated the chemotherapy effects. Further mechanistic investigation in vitro revealed that CRV modulates the interaction of breast cancer cells with the extracellular matrix (ECM) by disrupting focal adhesion, which was shown by scanning electron microscopy (SEM) and immunofluorescence. Moreover, CRV caused a decrease in β1-integrin expression and inhibited focal adhesion kinase (FAK) activation. FAK is one of the most important downstream activators of several metastatic processes, including MMP-2 mediated invasion and HIF-1α/VEGF angiogenesis stimulus, both of which were found to be reduced in MDA-MB-231 cells exposed to CRV. Our results provide new insight about targeting β1-integrin/FAK signaling pathway with CRV, which could be a new potential agent in the treatment of breast cancer.Copyright © 2023. Published by Elsevier B.V.