Abstract
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 BCL2 gene expression and upregulated the expression of the proapoptotic genes TP53 and BAX, 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.
Highlights
Colorectal cancer (CRC), one of the most common oncological disease worldwide, is an aggressive cancer with metastatic behavior [1,2,3]
No significant differences were observed between the two CRC cell lines regarding the IC50 values (Table 1), indicating that HT-29 and LoVo cells have a similar susceptibility to NEM and Cuban propolis (CP) effects
As already demonstrated by previous studies ([32] and refs. therein), considering NEM content in CP, the IC50 obtained in this study confirm that the antiproliferative effect of CP on CRC cell lines is mainly due to NEM
Summary
Colorectal cancer (CRC), one of the most common oncological disease worldwide, is an aggressive cancer with metastatic behavior [1,2,3]. 40%–60% of CRC patients develop metastases in other organs, in particular liver and lungs, which represent the main sites of CRC metastasis [4]. Tumor cells acquire the capacity to infiltrate blood or lymphatic vessels through an epithelial to mesenchymal transition (EMT) process, which increases cell migration and invasion, intravasation and extravasation. Taken together, these processes result in increased tumor aggressiveness and metastasis [8,9]. The proteins associated to cell migration and invasion, as well as the mechanisms involved in EMT, represent a pharmacological target for the treatment of CRC patients [10,11]
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