Colorectal and
pancreatic cancers remain important contributors to
cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L.) extracts and its components have been reported as natural potent antiproliferative agents against
cancer cells. However, to potentially apply rosemary as a complementary approach for
cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five
carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice) and in vitro against colon and
pancreatic cancer cells. We found that the antitumor effect of
carnosic acid together with
carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and
microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of
carnosic acid-rich rosemary extract as a complementary approach in colon and
pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive
biomarker to monitor rosemary anticancer effect.