Differences in ER-β expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.
The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980; 95% confidential interval (CI) 1.163-7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243-6.343; P = 0.013).
The effects of three fractions containing hydroxytyrosyl butanoate, octanoate, and oleate, named, respectively, lipophilic fractions 5, 6, and 7, and unreacted HTyr on the human colon cancer cell line HCT8-β8 engineered to overexpress estrogen receptor β (ERβ) were evaluated and compared to those of pure HTyr.
Spearman test revealed that PER1 and ER2 were significantly down-regulated in cancerous tissues (r=0.283; P<0.001) which was also confirmed by immunohistochemistry of specimens from 203 colon cancer patients in a TMA format.
In contrast, E2 could exert protective effects in cancer cells by activating apoptosis when the ERβ level prevails on that of ERα as in colon cancer cell lines.
These findings demonstrated that combined administration of Ad-ERβ with SOC-ICG-Der-01/NIR thermotherapy represents a promising colon cancer therapeutic strategy.
Thus upregulation of ER-β status by specific food-borne ER-ligands such as soy isoflavones could potentially be a dietary prevention or therapeutic strategy for colon cancer.
Our results show that ERbeta inhibits proliferation as well as colon cancer xenograft growth, probably as a consequence of ERbeta-mediated inhibition of cell-cycle pathways.