The effect of auraptene on folfox-resistant HT-29 colorectal adenocarcinoma cells

Investigations on cancer stem cells (CSCs) represent a novel challenge in cancer therapy. Our recent studies seem to indicate that auraptene (AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention.¹ Previously, we reported that AUR inhibits the growth of primary colon tumors in rodents.² However, nearly 50% of patients with colorectal cancer show recurrence of tumors that exhibit resistance to chemotherapy primarily due to the presence of CSCs. The current investigation was undertaken to determine whether AUR would prevent the growth and sphere (surrogate tumors) formation of FOLFOX-resistant colon cancer cells that are highly enriched in CSCs. Indeed, our results demonstrate that AUR (10µM) inhibits the growth and formation of colonospheres of FOLFOX-resistant colon cancer HT-29 cells in vitro. The corresponding parental cells were also similarly affected by AUR. The reduction in the growth and colon spheres formation in FOLFOX-resistant HT-29 was also associated with a concomitant decrease in phospho-epidermal growth factor receptor (pEGFR). These observations suggest that AUR could prevent the re-emergence of CSCs.

1. Genovese, S.; Epifano, F. Curr. Drug Targets 2011, 12, 381. 2. Kohno, H.; Suzuki, R.; Curini, M.; Epifano, F.; Maltese, F.; Prieto Gonzales, S.; Tanaka, T. Int. J. Cancer 2006 118, 2936.