Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy.
Chemistry and Health Faculty, Technical University of Machala, Ave. Panamericana Vía a Pasaje Km. 5 1/2, Machala 070101, Ecuador.
Int J Mol Sci. 2020 Mar 6;21(5):1827. doi: 10.3390/ijms21051827.
The majority of deaths related to colorectal cancer (CRC) are associated with the metastatic process. Alternative therapeutic strategies, such as traditional folk remedies, deserve attention for their potential ability to attenuate the invasiveness of CRC cells. The aim of this study is to investigate the biological activity of brown Cuban propolis (CP) and its main component nemorosone (NEM) and to describe the molecular mechanism(s) by which they inhibit proliferation and metastatic potential of 2 CRC cell lines, i.e., HT-29 and LoVo. Our results show that CP and NEM significantly decreased cell viability and inhibited clonogenic capacity of CRC cells in a dose and time-dependent manner, by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Furthermore, CP and NEM downregulated gene expression and upregulated the expression of the proapoptotic genes and , with a consequent activation of caspase 3/7. They also attenuated cell migration and invasion by inhibiting MMP9 activity, increasing E-cadherin and decreasing β-catenin and vimentin expression, proteins involved in the epithelial-mesenchymal transition (EMT). In conclusion NEM, besides displaying antiproliferative activity on CRC cells, is able to decrease their metastatic potential by modulating EMT-related molecules. These finding provide new insight about the mechanism(s) of the antitumoral properties of CP, due to NEM content.
大多数与结直肠癌 (CRC) 相关的死亡与转移过程有关。替代治疗策略，如传统的民间疗法，因其潜在的减弱 CRC 细胞侵袭能力而值得关注。本研究旨在研究棕色古巴蜂胶 (CP) 及其主要成分 nemorosone (NEM) 的生物学活性，并描述它们抑制 2 种 CRC 细胞系（HT-29 和 LoVo）增殖和转移潜能的分子机制。我们的结果表明，CP 和 NEM 以剂量和时间依赖性方式显著降低 CRC 细胞的活力并抑制其克隆形成能力，通过将细胞周期阻滞在 G0/G1 期并诱导细胞凋亡。此外，CP 和 NEM 下调 基因的表达，上调促凋亡基因 和 的表达，从而激活 caspase 3/7。它们还通过抑制 MMP9 活性、增加 E-钙粘蛋白和减少 β-连环蛋白和波形蛋白的表达来减弱细胞迁移和侵袭，这些蛋白参与上皮-间充质转化 (EMT)。总之，NEM 除了对 CRC 细胞具有抗增殖活性外，还能够通过调节 EMT 相关分子来降低其转移潜力。这些发现为 CP 的抗肿瘤特性的机制提供了新的见解，这归因于 NEM 的含量。
