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Antioxidant activities of the aqueous and ethanol extracts of pigeonpea [Cajanus cajan (L.) Millsp.] leaves, as well as petroleum ether, ethyl acetate, n-butanol and water fractions and the four main compounds separated from the ethanol extract, i.e. cajaninstilbene acid (3-hydroxy-4-prenylmethoxystilbene-2-carboxylic acid), pinostrobin, vitexin and orientin, were examined by a DPPH radical-scavenging assay and a β-carotene-linoleic acid test. In the DPPH system, the antioxidant activity of the ethanol extracts was superior to that of the aqueous extracts, with IC50 values were 242.01 and 404.91 µg/mL, respectively. Among the four fractions, the ethyl acetate one showed the highest scavenging activity, with an IC50 value of 194.98 µg/mL. Cajaninstilbene acid (302.12 µg/mL) and orientin (316.21 µg/mL) showed more efficient radical-scavenging abilities than pinostrobin and vitexin. In the β-carotene-linoleic acid test, the inhibition ratio (%) of the ethyl acetate fraction (94.13%±3.41%) was found to be the highest, being almost equal to the inhibition capacity of the positive control BHT (93.89%±1.45%) at 4 mg/mL. Pinostrobin (>500 µg/mL) and vitexin (>500 µg/mL) showed insignificant antioxidant activities compared with cajaninstilbene (321.53 µg/mL) and orientin (444.61 µg/mL). In general, the ethyl acetate fraction of the ethanol extract showed greater activity than the main compounds in both systems, such results might be attributed to the synergistic effects of the components. The antioxidant activities of all the tested samples were concentration-dependent. Based on the results obtained, we can conclude that the pigeonpea leaf extracts may be valuable natural antioxidant sources and are potentially applicable in both medicine and the healthy food industry.

Small cell lung cancer (SCLC) is a recalcitrant, aggressive neuroendocrine-type cancer for which little change to first-line standard-of-care treatment has occurred within the last few decades. Unlike nonsmall cell lung cancer (NSCLC), SCLC harbors few actionable mutations for therapeutic intervention. Lysine-specific histone demethylase 1A (LSD1 also known as KDM1A) inhibitors were previously shown to have selective activity in SCLC models, but the underlying mechanism was elusive. Here, we found that exposure to the selective LSD1 inhibitor ORY-1001 activated the NOTCH pathway, resulting in the suppression of the transcription factor ASCL1 and the repression of SCLC tumorigenesis. Our analyses revealed that LSD1 bound to the NOTCH1 locus, thereby suppressing NOTCH1 expression and downstream signaling. Reactivation of NOTCH signaling with the LSD1 inhibitor reduced the expression of ASCL1 and neuroendocrine cell lineage genes. Knockdown studies confirmed the pharmacological inhibitor-based results. In vivo, sensitivity to LSD1 inhibition in SCLC patient-derived xenograft (PDX) models correlated with the extent of consequential NOTCH pathway activation and repression of a neuroendocrine phenotype. Complete and durable tumor regression occurred with ORY-1001–induced NOTCH activation in a chemoresistant PDX model. Our findings reveal how LSD1 inhibitors function in this tumor and support their potential as a new and targeted therapy for SCLC.

Ten essential oils, namely, mint (Mentha spicata L., Lamiaceae), ginger (Zingiber officinale Rosc., Zingiberaceae), lemon (Citrus limon Burm.f., Rutaceae), grapefruit (Citrus paradisi Macf., Rutaceae), jasmine (Jasminum grandiflora L., Oleaceae), lavender (Mill., Lamiaceae), chamomile (Matricaria chamomilla L., Compositae), thyme (Thymus vulgaris L., Lamiaceae), rose (Rosa damascena Mill., Rosaceae) and cinnamon (Cinnamomum zeylanicum N. Lauraceae) were tested for their antibacterial activities towards Propionibacterium acnes and in vitro toxicology against three human cancer cell lines. Thyme, cinnamon and rose essential oils exhibited the best antibacterial activities towards P. acnes, with inhibition diameters of 40 ± 1.2 mm, 33.5 ± 1.5 mm and 16.5 ± 0.7 mm, and minimal inhibitory concentrations of 0.016% (v/v), 0.016% (v/v) and 0.031% (v/v), respectively. Time-kill dynamic procedures showed that OPEN ACCESSMolecules 2010, 15 3201 thyme, cinnamon, rose, and lavender essential oils exhibited the strongest bactericidal activities at a concentration of 0.25% (v/v), and P. acnes was completely killed after 5 min. The thyme essential oil exhibited the strongest cytotoxicity towards three human cancer cells. Its inhibition concentration 50% (IC 50 ) values on PC-3, A549 and MCF-7 tumor cell lines were 0.010% (v/v), 0.011% (v/v) and 0.030% (v/v), respectively. The cytotoxicity of 10 essential oils on human prostate carcinoma cell (PC-3) was significantly stronger than on human lung carcinoma (A549) and human breast cancer (MCF-7) cell lines.