An ethanolic extract of Anneslea f ragrans leaves showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition, with a PC 50 value of 9.6 μg/mL. Phytochemical investigation of this active extract led to the isolation of two new secondary metabolites, fragranones A (1) and B (2), along with 15 previously reported compounds. The structure elucidation of the new compounds was achieved by HRFABMS, acid hydrolysis, NMR, and ECD spectroscopic analysis. Fragranone A (1) is the first example of a rare natural product bearing an acetonide glucose moiety. Fragranone B ( 2) is representative of a rare class of natural products with a threonolactone unit linked to a chalcone through an ether linkage. The isolated compounds exhibited antiausterity activity against PANC-1 cells under nutrient-deprived conditions, and betulin ( 14) was found to be the most potent compound tested, with a PC 50 value of 8.4 μM. In addition, fragranone A (1) was found to suppress PANC-1 cancer cell migration in real time.

This study aimed to explore the antioxidant potential and antiviral activity of endophytic fungi which were isolated from healthy living tissues of medicinal plants. Endophytic strains (29 different taxa) were isolated from 18 Egyptian medicinal plants collected from Saint Katherine Protectorate, Egypt. The fungal endophytes were identified based on morphological characters. All isolates were identified as ascomycetes, except two Zygomycetes strains (Absidia corymbifera and Mucor fuscus). Isolated endophytes were cultivated on potato dextrose media. The fungal metabolites were extracted by ethyl acetate and examined for their biological activities. Among 99 total extracts, only Chaetomium globosum, which was isolated from Adiantum capillus, showed a promising DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activity (99% at 100 µg/mL). Fifteen extracts prohibited the reproduction of HSV-2 virus. On the other hand, the reproduction of VSV-virus was inhibited by sixteen endophytic extracts. The promising anti-(HSV-2 and VSV) extract of endophytic Pleospora tarda strain; that was originally isolated from the medicinal plant Ephedra aphylla, showed viral inhibitory activity of 40.7% and 15.2%, respectively. Two compounds, for which antiviral activates could be attributed, were isolated and identified as alternariol and alternariol-(9)-methyl ether using different NMR techniques from P. tarda extract. For the first time, we report here the ability of the endophytic fungus P. tarda to produce alternariol and alternariol-(9)-methyl ether. The results indicate that the endophytic fungi from medicinal plants are promising sources of bioactive compounds.

The antiausterity strategy is a promising approach for the discovery of lead compounds with unprecedented anticancer activities by targeting the tolerance of cancer cells to nutrition starvation. These agents are selectively cytotoxic under the tumor microenvironment-mimicking condition of nutrition starvation, without apparent toxicity in the normal nutrient-rich condition. In this study, an ethanol extract of Betula alnoides showed antiausterity activity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 13.2 μg/mL. Phytochemical investigation of this active extract led to the isolation of eight benzophenones (1–8), including six new compounds, named betuphenones A–F (2–7), and three known xanthones (9–11). The structure elucidation of the new compounds was achieved by HRFABMS, NMR, and ECD spectroscopic analyses. A plausible biogenetic pathway of the new compounds was proposed. Compounds 1–7 displayed antiausterity activity with PC50 values of 4.9–8.4 μM. Moreover, compounds 2 and 7 induced alterations in PANC-1 cell morphology under nutrient-deprived conditions and also inhibited PANC-1 colony formation under nutrient-rich conditions.

Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities.

Human pancreatic cancer cells display remarkable tolerance to nutrition starvation that help them to survive in a hypovascular tumor microenvironment, a phenomenon known as "austerity". The elucidation of agents countering this tolerance is an established antiausterity strategy in anticancer drug discovery. In this study, a Callistemon citrinus leaf extract inhibited the viability of PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived medium (NDM) with a PC 50 value of 7.4 μg/mL. Workup of this extract resulted in the isolation of three new meroterpenoids, callistrilones L−N (1−3), together with 14 known compounds (4−17). The structure elucidation of the new compounds was achieved by HRFABMS and by NMR and ECD spectroscopic analysis. The new compounds showed highly potent preferential cytotoxicity against PANC-1 cells with PC 50 values ranging from 10 to 65 nM in NDM. Of these, callistrilone L (1) inhibited PANC-1 cell migration and colony formation in a normal nutrient-rich condition. Callistrilone L (1) also strongly suppressed the migration of PANC-1 cells in real time. Mechanistically, 1 was found to inhibit the Akt/mTOR and autophagy activation pathway. Callistrilone L (1) and related meroterpenoids are promising leads for anticancer drug development based on the antiausterity strategy used in this work.

Human pancreatic tumor cells such as PANC-1 are known for their ability to tolerate nutrient starvation and thrive under the hypovascular tumor microenvironment, a phenomenon termed as 'austerity'. A search of agents that preferentially inhibit the cancer cell viability under the starvation condition without toxicity in the nutrientrich condition is a promising approach in anticancer drug discovery. In this study, a triterpene lactone, 3βhydroxy-13,28-epoxyurs-11-en-28-one (ursenolide), isolated from a Callistemon citrinus extract has shown strong preferential cytotoxicity against PANC-1 cells under nutrient starvation with PC 50 value of 0.4 μM. Ursenolideinduced rounding of PANC-1 cell morphology followed by rupture of the cell membrane leading to cell death. In a real-time cell migration study, ursenolide was found to inhibit PANC-1 cell migration significantly. Mechanistically, it inhibited GRP78 and GRP94 under the starvation condition suggesting inhibition of unfolded protein response (UPR), an adaptive process of cell survival during starvation. It also inhibited the phosphorylation of the key survival protein Akt and mTOR. Overall results suggested that ursenolide is a potential anticancer agent against pancreatic cancer.

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