Nitric Oxide Prevents Glioblastoma Stem Cells' Expansion and Induces Temozolomide Sensitization.

Glioblastoma multiforme (GBM) has high mortality and recurrence rates. Malignancy resilience is ascribed to Glioblastoma Stem Cells (GSCs), which are resistant to Temozolomide (TMZ), the gold standard for GBM post-surgical treatment. However, Nitric Oxide (NO) has demonstrated anti-cancer efficacy in GBM cells, but its potential impact on GSCs remains unexplored. Accordingly, we investigated the effects of NO, both alone and in combination with TMZ, on patient-derived GSCs. Experimentally selected concentrations of diethylenetriamine/NO adduct and TMZ were used through a time course up to 21 days of treatment, to evaluate GSC proliferation and death, functional recovery, and apoptosis. Immunofluorescence and Western blot analyses revealed treatment-induced effects in cell cycle and DNA damage occurrence and repair. Our results showed that NO impairs self-renewal, disrupts cell-cycle progression, and expands the quiescent cells' population. Consistently, NO triggered a significant but tolerated level of DNA damage, but not apoptosis. Interestingly, NO/TMZ cotreatment further inhibited cell cycle progression, augmented G0 cells, induced cell death, but also enhanced DNA damage repair activity. These findings suggest that, although NO administration does not eliminate GSCs, it stunts their proliferation, and makes cells susceptible to TMZ. The resulting cytostatic effect may potentially allow long-term control over the GSCs' subpopulation.

Ulva intestinalis Extract Acts as Biostimulant and Modulates Metabolites and Hormone Balance in Basil (Ocimum basilicum L.) and Parsley (Petroselinum crispum L.).

Natural elicitors from macroalgae may affect plant secondary metabolites. Ulvan is a sulfated heteropolysaccharide extracted from green seaweed, acting as both a plant biotic protecting agent, and a plant elicitor, leading to the synthesis of signal molecules. In this work, the aqueous extract of Ulva intestinalis L., mainly composed of ulvan, was used as foliar-spraying treatment and its eliciting effect was investigated in basil (Ocimum basilicum L.) and parsley (Petroselinum crispum L.). Antioxidant metabolites (polyphenols and carotenoids), volatile compounds (both in headspace emissions and hydrodistilled essential oils), and hormones (jasmonic acid, salicylic acid, salicylic acid 2-O-ß-D-glucoside, abscisic acid, and azelaic acid) were quantified. The foliar-spraying treatment with U. intestinalis extract increased salicylic acid and its ß-glucoside in parsley; in basil, it induced the accumulation of jasmonic and abscisic acids, indicating the presence of a priming effect. In basil, the elicitation caused a change of the essential oil (EO) chemotype from methyl eugenol/eugenol to epi-α-cadinol and increased sesquiterpenes. In parsley EO it caused a significant accumulation of 1,3,8-p-menthatriene, responsible of the typical "parsley-like" smell. In both species, the phenylpropanoids decreased in headspace and EO compositions, while the salicylic acid concentration increased; this could indicate a primarily defensive response to U. intestinalis extract. Due to the evidenced significant biological activity, U. intestinalis extract used as an elicitor may represent a suitable tool to obtain higher amounts of metabolites for optimizing plant flavor metabolites.