AUTOPHAGY FLUX MODULATION BY A CAROTENOID-ENRICHEDEXTRACT FROM THE PUMPKIN CUCURBITA MOSCHATA ONHUMAN CHRONIC LYMPHOCYTIC LEUKEMIA CELL LINE

Introduction: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in adult population and chemotherapy resistance occurs in 15e30% of patients with elevated genomic complexity. Apoptosis resistance and induction of a protective form of autophagy are possible explanations of the poor responsivity of CLL to conventional and novel therapeutic drugs. Given the difficulties to maintain in culture B-CLL lymphocytes, the HG3 cell line represents an interesting preclinical model to study the effects of natural bioactive molecules or extracts derived from food matrix as potential, chemo-sensitizers in CLL. Objective: A previous study demonstrated the induction of "not-protective" autophagy on osteosarcoma and colon adenocarcinoma cell lines after prolonged treatment with a carotenoid-enriched extract (CE) obtained from the pumpkin Cucurbita moschata, variety "long of Naples". To extend and confirm these data, the present communication focuses on the anti-proliferative effect of the same extract in HG3 cell line derived from EBV immortalization of B-CLL cells. Results: CE was obtained from pumpkin by supercritical CO2 extraction and delivered to HG3 cells in combination with foetal bovine serum. After 96 h, we detected a 40% delay in cell proliferation compared to untreated cells, without signs of cytotoxicity. This delay was due to p27/KIP1 over-expression and modulation of autophagic flux, measured by different autophagy markers (LC3II; p62) and 30% autophagosome intracellular increase. Conclusions: The results obtained will be discussed at the light of the functional cross-talk between the modulation of the autophagy flux by the CE extract and the retard in cell growth observed in HG3 cells, as an opportunity to prolong the asymptomatic phase of CLL before disease occurrence.