Bioactive Compounds from Posidonia oceanica (L.) Delile Impair Malignant Cell Migration through Autophagy Modulation

Abstract

Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica, showed the ability to impair HT1080 cell migration by targeting both expression and activity of gelatinases. Commonly, the lack of knowledge about the mechanism of action of phytocomplexes may be an obstacle regarding their therapeutic use and development. The aim of this study was to gain insight into the molecular signaling through which such bioactive compounds impact on malignant cell migration and gelatinolytic activity. The increase in autophagic vacuoles detected by confocal microscopy suggested an enhancement of autophagy in a time and dose dependent manner. This autophagy activation was further confirmed by monitoring pivotal markers of autophagy signaling as well as by evidencing an increase in IGF-1R accumulation on cell membranes. Taken together, our results confirm that the P. oceanica phytocomplex is a promising reservoir of potent and cell safe molecules able to defend against malignancies and other diseases in which gelatinases play a major role in progression. In conclusion, the attractive properties of this phytocomplex may be of industrial interest in regard to the development of novel health-promoting and pharmacological products for the treatment or prevention of several diseases.

Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration

“…Single batch of P. oceanica extract was dissolved in 0.5 mL of EtOH/H 2 O (70:30 v/v) before to use and hereafter referred to as POE. Freshly-dissolved POE was characterized for total polyphenols and carbohydrates content and antioxidant and radical scavenging activities, according to previously described methods [6,7]. Drug: extract ratio (D.E.R) was 8:1.…”

“…The wound healing assay [6,7] was used to test SH-SY5Y cell migration. Cells were plated in 6-well plate at 5 × 10 5 cells/well density in complete medium.…”

“…POE has been characterized for the total content of polyphenols and carbohydrates and for its antioxidant and radical scavenging activities as described in previous works [6][7][8] and reported in Table S1 of Supplementary material.…”

“…POE and POE-loaded into nanoformulations (NP-POE and PM-POE) were tested on human neuroblastoma SH-SY5Y cell line, at the final concentration of 3 μg/mL according to data previously obtained on POE bioactivities [6][7][8].…”

“…Moreover, the hydroalcoholic extract of P. oceanica (POE) was found to prevent human cancer cell migration with non-toxic mechanism of action. Specifically, the P. oceanica phytocomplex has been proven to reduce the motility of human fibrosarcoma cells and the activity of metalloproteases (MMP-2/9) through the activation of a transient autophagic process without any detectable effect on cell viability [6,7]. The anti-inflammatory mechanism of P. oceanica phytocomplex was recently elucidated [8].…”