A Carotenoid Extract from a Southern Italian Cultivar of Pumpkin Triggers Nonprotective Autophagy in Malignant Cells.

Maria Russo,Stefania Bilotto,Marcello Salvatore Lenucci,Rita Patrizia Aquino,Carmela Spagnuolo,Gian Luigi Russo,Miriana Durante,Maria Grazia Volpe,Stefania Moccia,Giovanni Mita

doi:10.1155/2017/7468538

Abstract

Carotenoids, including β-carotene, lycopene, and derivatives, such as retinoic acid, have been studied for their significant antiproliferative and differentiating activity on cancer cells in experimental models and in clinics. We are presenting here data on the mechanism of action of a carotenoid-enriched extract obtained from the pumpkin Cucurbita moschata, variety “long of Naples,” on two malignant human cell lines, Caco-2 and SAOs, derived from a colon adenocarcinoma and an osteosarcoma, respectively. The carotenoid extract has been obtained from pumpkin pulp and seeds by supercritical CO2 extraction and employed to prepare oil-in-water nanoemulsions. The nanoemulsions, applied at a final carotenoid concentration of 200–400 μg/ml, were not cytotoxic, but induced a delay in cell growth of about 40% in both SAOs and Caco-2 cell lines. This effect was associated with the activation of a “nonprotective” form of autophagy and, in SAOs cells, to the induction of cell differentiation via a mechanism that involved AMPK activation. Our data suggest the presence of a pool of bioactive compounds in the carotenoid-enriched extract, acting additively, or synergistically, to delay cell growth in cancer cells.

Highlights

In the last two decades, the anticancer properties of phytochemicals raised the interest of many scientists, preclinical and clinical studies often generated contradictory results
The present study investigates the capacity of a supercritical CO2 (SC-CO2) extract enriched in carotenoids obtained from Cucurbita moschata sp. to regulate cell growth in human malignant cells
Caco-2 and SAOs cells were incubated with CEN, corresponding to 400 and 200 μg/ml of carotenoid-enriched extract (w/v), respectively, at different times

Summary

Introduction

In the last two decades, the anticancer properties of phytochemicals raised the interest of many scientists, preclinical and clinical studies often generated contradictory results. A recent meta-analysis of prospective studies suggested a positive correlation between dietary intake of phytochemicals (800–600 mg/die) and reduced risk of cancer, cardiovascular diseases, and all causes of mortality [2]. Carotenoids represent one of the most largely studied class of phytochemicals, since their biological activities have been associated with positive outcomes in terms of human health [5]. Carotenoids include about 600 isoprenoid compounds containing up to 15 conjugated double bonds divided into the two major groups of carotenes and xanthophylls; the former are pure hydrocarbons such as β-carotene, while the latter include their oxygenated derivatives, such as zeaxanthin. About 50 carotenoids are present in the human diet, but only 20 have been identified in the human plasma, among these, the most represented are β-carotene and α-carotene, lycopene, and cryptoxanthin [7, 8].

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