Kalanchoe pinnata (Lam.) Pers. Leaf ethanolic extract exerts selective anticancer activity through ROS-induced apoptotic cell death in human cancer cell lines.

BACKGROUND: The leaves of Kalanchoe pinnata (Lam.) Pers. (K. pinnata), a succulent plant native to tropical regions, are used as a medicinal alternative against cancer in several countries worldwide; however, its therapeutic potential to fight cancer has been little addressed. In this study, we analyzed the phytochemical content, antioxidant capacity, and selectivity of K. pinnata leaf ethanolic extract against different human cancer cell lines in vitro. METHODOLOGY: This study subjected the ethanolic extract to enzymatic assays to quantify the phytochemical content (phenolics, flavonoids, and anthraquinones) and its radical scavenging and iron-reducing capacities. Also, the phytoconstituents and major phenolic compounds present in the extract's subfractions were identified by GC-MS, HPLC, and NMR. Human cancer (MCF-7, PC-3, HT-29) and normal colon (CoN) cell lines were treated with different concentrations of K. pinnata leaf ethanolic extract, and the changes in cell proliferation (sulforhodamine B assay), caspases activity (FITC-VAD-FMK reporter), mitochondrial membrane potential (MMP, rhodamine 123 assay), chromatin condensation/fragmentation (Hoechst 33342 stain), and ROS generation (DCFH2 probe assay) were assessed. RESULTS: The results showed that the K. pinnata leaf ethanolic extract is rich in phytoconstituents with therapeutic potential, including phenols (quercetin and kaempferol), flavonoids, fatty acid esters (34.6% of the total composition), 1- triacontanol and sterols (ergosterol and stigmasterol, 15.4% of the total composition); however, it presents a poor content of antioxidant molecules (IC50 = 27.6 mg/mL for H2O2 scavenging activity vs. 2.86 mg/mL in the case of Trolox). Notably, the extract inhibited cell proliferation and reduced MMP in all human cell lines tested but showed selectivity for HT-29 colon cancer cells compared to CoN normal cells (SI = 8.4). Furthermore, ROS generation, caspase activity, and chromatin condensation/fragmentation were augmented significantly in cancer-derived cell lines, indicating a selective cytotoxic effect. CONCLUSION: These findings reveal that the K. pinnata leaf ethanolic extract contains several bioactive molecules with therapeutic potential, capable of displaying selective cytotoxicity in different human cancer cell lines.

Feeding Performance of Argentine Stem Weevil Is Reduced by Peramine from Perennial Ryegrass Infected with Endophyte Fungus.

One of the primary supports for extensive agriculture is pasture, which can suffer severe damage from insects including the Argentine stem weevil, Listronotus bonariensis. The main control method has been the infection of ryegrass with an endophyte fungus, forming a symbiotic association that produces alkaloids. In this study, we evaluated the impact of endophyte and peramine production on the weight of L. bonariensis across seven unnamed lines (LE161-LE167), and two Lolium perenne cultivars: Jumbo and Alto AR1. L. bonariensis adults fed on leaves from LE164, LE166, and ALTO AR1 showed weight losses of 13.3%, 17.1% and 18.2%, respectively. Similarly, the corresponding alkaloidal extract from LE164, LE166, and ALTO AR1 exhibited an antifeedant effect on L. bonariensis adults in laboratory assays, as observed through weight loss or low weight gain (-12.5%, 8.8% and 4.9%, respectively). Furthermore, one alkaloid, peramine, also elicited an antifeedant effect when incorporated into an artificial diet. Liquid chromatographic analysis of the alkaloid extract revealed that peramine was present in LE164, LE166 and ALTO AR1 in amounts ranging from 46.5-184.2 ng/g. Peramine was not detected in Jumbo and the remaining experimental lines. These data suggest that L. bonariensis were susceptible to peramine produced from endophyte infection in experimental lines LE164 and LE166, as well as ALTO AR1, affecting their feeding behavior.

Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol.

In this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents.

Infection of perennial ryegrass (Lolium perenne) by an endophyte fungus (Neotyphodium lolii) decreases the abundance and diversity of predators and parasitoids

ABSTRACT Perennial ryegrass is one of the most important food sources in animal production. However, several pests affect this crop, and one of the primary control strategies is the symbiotic relationships between ryegrass endophyte fungi. This fungus produces alkaloids that exhibit toxic activity against arthropods. Furthermore, the effect of fungi may extend to higher trophic levels, including predators (spiders and/or insects), decreasing their abundance and diversity. Given the importance of spiders and insects as predators, whether the symbiotic interaction between perennial ryegrass and endophyte fungus reduces the abundance and diversity of predators pose an important question. To address this question, natural enemies in perennial ryegrass were collected and analyzed over a year, and the percentage of endophyte fungus was evaluated by the presence of hyphae from two ryegrass cultivars, Jumbo (E-) and Alto AR1 (E+). We observed an 80% endophyte infection rate for (E+) and 0% for (E-). Moreover, 222 individual spiders corresponding to 10 families were identified in both perennial ryegrasses, including 209 individuals for (E-) and 13 for (E+). The most abundant spider family was Lycosidae, representing 71.17% of the total spiders. In addition, 65 insects were collected, corresponding to 6 families, with Carabidae being the most abundant. Furthermore, the Simpson index indicated the dominance of the family Lycosidae. Overall, spider and insect abundance and diversity were reduced in (E+), suggesting a negative effect of the endophyte on predator populations.

Distribution and ultrastructure of the antennal sensilla of the grape weevil Naupactus xanthographus (Coleoptera: Curculionidae).

The grape weevil, Naupactus xanthographus Germar (Coleoptera: Curculionidae), is a polyphagous insect native to southern South America that causes considerable damage in grape and other fruit species. In this study, the morphology and ultrastructure of the antennae and the antennal sensilla of N. xanthographus were investigated using scanning electron microscopy and transmission electron microscopy. The antennae consist of a scape, a pedicel, a funicle, and a zone called the "club," which are all formed by a total of 12 antennomers. Different types of sensilla were observed: sensilla trichoidea, sensilla chaetica type 1 and 2, sensilla basiconica, and sensilla rod-like. No sexual dimorphism was observed. The possible functions of the sensilla are discussed in relation to their morphology and ultrastructure.

Biological Activity of the Larval Secretion of Chilecomadia valdiviana.

The carpenter worm, Chilecomadia valdiviana (Lepidoptera: Cossidae), is a polyphagous insect native to Chile that is associated with trees and bushes, including economically important species such as eucalyptus, avocado, and apples. We used a Y-olfactometer to analyze the olfactory responses of larvae to conspecific larvae, hexane extracts of larvae, and synthetic samples of the major components present in the extract (i.e., (Z)-5,13-tetradecadienyl acetate, (Z)-5-tetradecenyl acetate, and dodecyl acetate). The results obtained provide empirical evidence that (Z)-5,13-tetradecadienyl acetate is used as an aggregation pheromone by the larvae. The results are discussed in view of the existing information.