A carotenoid-enriched extract from pumpkin delays cell proliferation in a human chronic lymphocytic leukemia cell line through the modulation of autophagic flux

Abstract

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in the adult population. From an asymptomatic state, which can lay for years, CLL rapidly evolves becoming fatal. Apoptosis resistance and induction of a protective form of autophagy are possible explanations of the poor responsivity of CLL to conventional and innovative therapeutic drugs. Carotenoids, including α- and β-carotene, lycopene, and derivatives, such as retinoic acid, have been studied for their significant antiproliferative and differentiating activity in cancer. Here, we report that a carotenoid-enriched extract (CE) obtained from pumpkin by supercritical CO2 extraction showed an anti-proliferative effect on HG3 cell line derived from human B-CLL cells. CE induced a 40% delay in cell proliferation compared to untreated cells, without signs of cytotoxicity. This delay was associated with p27Kip1 over-expression, AMPK activation and modulation of autophagy flux. In HG3 cells treated with CE, we detected a 30% autophagosome intracellular increase and changes in the expression of canonical biochemical markers of autophagy (LC3-II, p62). These results suggest the presence in the CE of a pool of bioactive carotenoids acting additively or synergistically in retarding cancer cell growth.

Keywords

• Chronic lymphocytic leukemia
• Autophagy
• Carotenoids
• HG3 cell line