In conclusion, KB-34 inhibits the TPA-stimulated metastatic potential of HT-29 cells by induction of HO-1 and may be a promising anti-cancer agent in chemotherapeutic strategies for CRC.
The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.
HMOX1A-413T was not associated with CRC risk and no interactions with diet or lifestyle were identified in this large, prospective cohort with high meat intake.
However, the nuclear HO-1 expression is apparently higher in moderately/poorly differentiated CRC than well-differentiated CRC probably suggesting a new mechanism of function involved in HO-1 in cancer.
These results suggested that the mechanism underlying the acquisition of 5-FU resistance in CRC involves the upregulation of Nrf2 and HO-1 expression via epigenetic modifications of DNA demethylation.
No association between CRC risk and individual HMOX1 gene variants was observed, although a diplotype analysis revealed an increased risk for a specific HMOX1 genotype combination.