indicaxanthin and Neoplasms

Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory and anti-tumoral ones and favored by its high bioavailability. Moreover, biochemical and molecular modelling investigations are aimed to identify the pharmacological targets the compound is able to interact with and to address the challenging development in the future research.

Topics: Animals; Antineoplastic Agents, Phytogenic; Betaxanthins; Biological Products; Blood-Brain Barrier; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fruit; Humans; Inflammation; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Structure; Neoplasms; Neuroprotective Agents; Opuntia; Phytochemicals; Pyridines; Structure-Activity Relationship

Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydrolase (LTA4H), Phosphoserine phosphatase (HPSP), Phosphodiesterase 4D (PDE4D), AMPA receptor (GluA3 and GluA2 subunits) and Kainate receptor (GluK1 isoform) as potential targets for Indicaxanthin. These targets are implicated in neuromodulation, and inflammatory regulation, normally expressed mostly in the CNS, and expressed (or overexpressed) in cancer tissues (i.e. breast, thyroid, and prostate cancer cells). Moreover, this study provides qualitative and quantitative information about dynamic interactions of Indicaxanthin at the binding site of target proteins, through molecular dynamics simulations and MM-GBSA.

Topics: Antineoplastic Agents, Phytogenic; Betaxanthins; Binding Sites; Data Mining; Enzyme Inhibitors; Humans; Molecular Docking Simulation; Neoplasm Proteins; Neoplasms; Opuntia; Pyridines