Abstract

Papaya (Carica papaya L.) is a fleshy fruit with a rapid pulp softening during ripening. Ripening events are accompanied by gradual depolymerization of pectic polysaccharides, including homogalacturonans, rhamnogalacturonans, arabinogalactans, and their modified forms. During intermediate phases of papaya ripening, partial depolymerization of pectin to small size with decreased branching had enhanced pectin anti-cancer properties. These properties were lost with continued decomposition at later phases of ripening. Pectin extracted from intermediate phases of papaya ripening markedly decreased cell viability, induced necroptosis, and delayed culture wound closing in three types of immortalized cancer cell lines. The possible explanation for these observations is that papaya pectins extracted from the third day after harvesting have disrupted interaction between cancer cells and the extracellular matrix proteins, enhancing cell detachment and promoting apoptosis/necroptosis. The anticancer activity of papaya pectin is dependent on the presence and the branch of arabinogalactan type II (AGII) structure. These are first reports of AGII in papaya pulp and the first reports of an in vitro biological activity of papaya pectins that were modified by natural action of ripening-induced pectinolytic enzymes. Identification of the specific pectin branching structures presents a biological route to enhancing anti-cancer properties in papaya and other climacteric fruits.

Highlights

  • Dietary fiber are generally considered carbohydrates that are incompletely processed by human digestive enzymes[1], but can provide health benefits[2], such as lowering the risk of colorectal cancer development[3]

  • Papaya pectin previously isolated from different ripening stages seems to have a promising composition concerning the presence of galactans, arabinans, rhamnogalacturonan type I (RG-I) and HG structures[24,26]

  • To explore the biological activity of papaya pectin naturally modified by ripening phenomenon, three cancer cell lines were treated with water-soluble papaya pectin extracted from fruits in distinct ripening stages

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Summary

Introduction

Dietary fiber are generally considered carbohydrates that are incompletely processed by human digestive enzymes[1], but can provide health benefits[2], such as lowering the risk of colorectal cancer development[3]. Especially the modified ones, have been associated with anti-cancer activity in both in vitro and in vivo studies, such as the reduction of cell proliferation, migration, adhesion, and the induction of apoptosis[6,7,8,9,10]. Increased action of cell wall degrading enzymes during ripening of papaya and consequent decrease of pectin molecular weight[27] might naturally modify pectin structures possibly increasing pectin’s anti-cancer activity. The present study aimed to characterize and to evaluate pectin isolated from papaya fruits harvested at different ripening stages to investigate the relationship between changes in pectin’s structure and their anti-proliferative activity on three cancer cell lines

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