Ripe papaya pectins inhibit the proliferation of colon cancer spheroids and the formation of chemically induced aberrant crypts in rats colons.

Pectins are a class of soluble polysaccharides that can have anticancer properties through several mechanisms. This study aimed to characterize the molecular structure of water-soluble fractions (WSF) derived from ripe and unripe papayas and assess their biological effects in two models: the 3D colon cancer spheroids to measure cell viability and cytotoxicity, and the in vivo model to investigate the inhibition of preneoplastic lesions in rats. WSF yield was slightly higher in ripe papaya, and both samples mainly consisted of pectin. Both pectins inhibited the growth of colon cancer HT29 and HCT116 spheroids. Unripe pectin disturbed HT29/NIH3T3 spheroid formation, decreased HCT116 spheroid viability, and increased spheroid cytotoxicity. Ripe pectin had a more substantial effect on the reduction of spheroid viability for HT29 spheroids. Furthermore, in vivo experiments on a rat model revealed a decrease in aberrant crypt foci (ACF) formation for both pectins and increased apoptosis in colonocytes for ripe papaya pectins. The results suggest potential anticancer properties of papaya pectin, with ripe pectin showing a higher potency.

Unveiling Plant-Based Pectins: Exploring the Interplay of Direct Effects, Fermentation, and Technological Applications in Clinical Research with a Focus on the Chemical Structure.

Pectin, a plant-derived polysaccharide, possesses immense technological and biological application value. Several variables influence pectin's physicochemical aspects, resulting in different fermentations, interactions with receptors, and other functional properties. Some of those variables are molecular weight, degree of methylation and blockiness, and monosaccharide composition. Cancer cell cytotoxicity, important fermentation-related byproducts, immunomodulation, and technological application were found in cell culture, animal models, and preclinical and clinical assessments. One of the greater extents of recent pectin technological usage involves nanoencapsulation methods for many different compounds, ranging from chemotherapy and immunotherapy to natural extracts from fruits and other sources. Structural modification (modified pectin) is also utilized to enhance the use of dietary fiber. Although pectin is already recognized as a component of significant importance, there is still a need for a comprehensive review that delves into its intricate relationships with biological effects, which depend on the source and structure of pectin. This review covers all levels of clinical research, including cell culture, animal studies, and clinical trials, to understand how the plant source and pectin structures influence the biological effects in humans and some technological applications of pectin regarding human health.

Systems biology applied to the study of papaya fruit ripening: the influence of ethylene / Biologia de sistemas aplicada ao estudo do amadurecimento de mamões: a influência do etileno

Fruit ripening is a biochemical process that results in flavor, odor, texture, and color suitable for human consumption, in addition to providing access to important nutrients. Although ripening promotes sensory and nutritional increases in fruits, there is also an increased susceptibility to physical damage, as is the case with papaya. These transformations occur due to changes in gene expression patterns at different stages of maturity, whose control and coordination result from the combined action of plant hormones, especially ethylene. As the action of this hormone in the regulation of gene expression is still elusive, this dissertation sought to address the global analysis of the transcriptome in an overview study of molecular processes involved in the ripening of ethylene-treated and non-treated papaya. Transcription factors related to ethylene synthesis and signaling had increased activity towards exogenous-ethylene treatment. Consequently, ethylene-induced enzymes had their coding genes differentially expressed, like genes related to the synthesis of carotenoids, linalool, and vitamins, which increase color, aroma, and antioxidant activity, respectively. Metabolic pathways related to the synthesis of sugars were suppressed while genes encoding the enzyme responsible for sucrose synthesis maintained a basal expression, showing that the accumulation of sugars occurs before the ripening process. The firmness of the peel and pulp of the fruits were strongly influenced by the treatment with ethylene and by the time of the experiment, suffering the action of numerous enzymes related to the degradation of the cell wall. The main enzyme responsible for softening the pulp was polygalacturonase, together with the activity of other pectinases and cellulases. In contrast to the need for the pre-climacteric action of pectate lyase and pectinesterase reported in other fleshy fruits, such as tomatoes and strawberries, papaya did not show a significant difference in their expression. The meta-analysis of several papaya ripening transcriptomes confirmed the expression profile observed in the previous RNA-seq, besides providing statistical enrichment to the biological narratives. Finally, the present study gathered a range of robust information on the gene regulation of the papaya ripening process, which opens possibilities for future approaches to transcriptomic analysis and validates the use of papaya as a model for such studies

O amadurecimento de frutos é um processo bioquímico que resulta em sabor, odor, textura e cor adequados para o consumo humano, além de propiciar o acesso a nutrientes importantes. Apesar do amadurecimento promover incrementos sensoriais e nutricionais nos frutos, ocorre também um aumento da suscetibilidade a danos físicos, como é o caso do mamão. Essas transformações ocorrem devido às alterações nos padrões de expressão gênica nos diferentes estádios de amadurecimento, cujo controle e coordenação decorrem da ação combinada de hormônios vegetais, principalmente do etileno. Como a ação deste hormônio na regulação da expressão gênica ainda é elusiva, a presente dissertação buscou abordar a análise global do transcriptoma em um amplo estudo dos processos moleculares envolvidos no amadurecimento de mamões tratados e não tratados com etileno. Os fatores de transcrição relacionados com a síntese e a sinalização do etileno tiveram sua atividade aumentada perante o tratamento exógeno com etileno. Consequentemente, as enzimas reguladas por esse hormônio tiveram seus genes de codificação expressos diferencialmente, como foi o caso de genes relacionados à síntese de carotenoides, linalool e vitaminas, que atuam no aumento da cor, aroma e atividade antioxidante, respectivamente. Vias metabólicas relacionadas com à síntese de açúcares foram reprimidas enquanto genes codificantes da enzima responsável pela síntese de sacarose mantiveram uma expressão basal, evidenciando que o acúmulo de açúcares ocorre antes do processo de amadurecimento. A firmeza da casca e da polpa dos frutos foram fortemente influenciadas pelo tratamento com etileno e pelo tempo de experimento, sofrendo ação de inúmeras enzimas relacionadas com a degradação da parede celular. A principal enzima responsável pelo amolecimento da polpa foi a poligalacturonase, em conjunto com a atividade de outras pectinases e celulases. Em contraste com a necessidade da ação pré-climatérica da pectato liase e da pectinesterase relatada em outras frutas carnosas, como tomates e morangos, o mamão não apresentou uma diferença significativa na expressão das mesmas. A meta-análise de diversos transcriptomas do amadurecimento do mamão reafirmaram o perfil de expressão observado no RNA-seq, além de prover enriquecimento estatístico às narrativas biológicas. Por fim, o presente estudo reuniu uma gama de informações robustas sobre a regulação gênica do processo de amadurecimento do mamão papaia, o que abrange a possibilidade para futuras abordagens de análise transcriptomica e valida o uso do mamão como modelo para tais estudos

Systems Biology Applied to the Study of Papaya Fruit Ripening: The Influence of Ethylene on Pulp Softening.

Papaya is a fleshy fruit that undergoes fast ethylene-induced modifications. The fruit becomes edible, but the fast pulp softening is the main factor that limits the post-harvest period. Papaya fast pulp softening occurs due to cell wall disassembling coordinated by ethylene triggering that massively expresses pectinases. In this work, RNA-seq analysis of ethylene-treated and non-treated papayas enabled a wide transcriptome overview that indicated the role of ethylene during ripening at the gene expression level. Several families of transcription factors (AP2/ERF, NAC, and MADS-box) were differentially expressed. ACO, ACS, and SAM-Mtase genes were upregulated, indicating a high rate of ethylene biosynthesis after ethylene treatment. The correlation among gene expression and physiological data demonstrated ethylene treatment can indeed simulate ripening, and regulation of changes in fruit color, aroma, and flavor could be attributed to the coordinated expression of several related genes. Especially about pulp firmness, the identification of 157 expressed genes related to cell wall metabolism demonstrated that pulp softening is accomplished by a coordinated action of several different cell wall-related enzymes. The mechanism is different from other commercially important fruits, such as strawberry, tomato, kiwifruit, and apple. The observed behavior of this new transcriptomic data confirms ethylene triggering is the main event that elicits fast pulp softening in papayas.