No abstract

No abstract

Graphical abstract

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype. Among young females, TNBC is the leading cause of cancer-related mortalities. Recently, long noncoding RNAs (lncRNAs) are representing a promising pool of regulators for tuning the aggressiveness of several solid malignancies. However, this still needs further investigations in TNBC. The main aim of this study is to unravel the expression pattern of sONE lncRNA and its mechanistic role in TNBC. Results showed that sONE is restrictedly expressed in TNBC patients; its expression level is inversely correlated with the aggressiveness of the disease. sONE acts as a posttranscriptional regulator to endothelial nitric oxide synthase (eNOS) and thus affecting eNOS-induced nitric oxide (NO) production from TNBC cells measured by Greiss reagent. Mechanistically, sONE is a potential tumor suppressor lncRNA in TNBC cells; repressing cellular viability, proliferation, colony-forming ability, migration, and invasion capacities of MDA-MB-231. Furthermore, sONE effects were found to be extended to affect the maestro tumor suppressor TP53 and the oncogenic transcription factor c-Myc. Knocking down of sONE resulted in a marked decrease in TP53 and increase in c-Myc and consequently altering the expression status of their downstream tumor suppressor microRNAs (miRNAs) such as miR-34a, miR-15, miR-16, and let-7a. In conclusion, this study highlights sONE as a downregulated tumor suppressor lncRNA in TNBC cells acting through repressing eNOSinduced NO production, affecting TP53 and c-Myc proteins levels and finally altering the levels of a panel of tumor suppressor miRNAs downstream TP53/c-Myc proteins. K E Y W O R D S eNOS, long noncoding RNAs, microRNAs, nitric oxide, sONE, triple-negative breast cancer SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Youness RA, Hafez HM, Khallaf E, Assal RA, Abdel Motaal A, Gad MZ. The long noncoding RNA sONE represses triple-negative breast cancer aggressiveness through inducing the expression of miR-34a, miR-15a, miR-16, and let-7a.

Adenylyl cyclase Rv2212 from Mycobacterium tuberculosis has a domain composition identical to the pH‐sensing isoform Rv1264, an N‐terminal regulatory domain and a C‐terminal catalytic domain. The maximal velocity of Rv2212 was the highest of all 10 mycobacterial cyclases investigated to date (3.9 µmol cAMP·mg−1·min−1), whereas ATP substrate affinity was low (SC50 = 2.1 mm ATP). Guanylyl cyclase side activity was absent. The activities and kinetics of the holoenzyme and of the catalytic domain alone were similar, i.e. in distinct contrast to the Rv1264 adenylyl cyclase, in which the N‐terminal domain is autoinhibitory. Unsaturated fatty acids strongly stimulated Rv2212 activity by increasing substrate affinity. In addition, fatty acids greatly enhanced the pH sensitivity of the holoenzyme, thus converting Rv2212 to a pH sensor adenylyl cyclase. Fatty acid binding to Rv2212 was modelled by homology to a recent structure of the N‐terminal domain of Rv1264, in which a fatty acid‐binding pocket is defined. Rv2212 appears to integrate three cellular parameters: ATP concentration, presence of unsaturated fatty acids, and pH. These regulatory properties open the possibility that novel modes of cAMP‐mediated signal transduction exist in the pathogen.

Context: Solidago virgaurea L. (Asteraceae) is traditionally used as an anti-inflammatory for the treatment of various symptoms including cystitis. However, little is known concerning the constituents responsible for this activity and the mechanism of their action. Objective: To assess the anti-inflammatory activity of the phenolic-rich fraction of S. virgaurea aerial parts in rats, isolate and assess the activity of the major compounds present. Materials and methods: An HPLC method was developed for the analysis of the phenolic-rich fraction (EtFr). The in vivo anti-inflammatory activity of the EtFr and four isolated compounds (at 25 and 50 mg/kg) were assessed in adult male rats using the carrageenan-induced rat paw oedema model. The levels of the pro-inflammatory cytokines (TNF-a and IL-1b) were measured using ELISA. Results: 3,5-O-Dicaffeoylquinic acid (1), 3,4-O-dicaffeoylquinic acid (2), 3,4,5-O-tricaffeoylquinic acid (3) and 4,5-O-dicaffeoylquinic acid (4) were isolated from EtFr. Compound 3 (50 mg/kg) showed a highly significant activity in inhibiting the oedema volume after 3 h (88% of the activity of indomethacin at 10 mg/kg). The EtFr and the isolated compounds largely inhibited the excessive production of the inflammatory mediators TNF-a and IL-1b. Discussion and conclusion: This is the first report of 3,4,5-tri-O-caffeoylquinic acid (3) in Solidago species. The tricaffeoylquinic acid (3) showed a significantly higher activity than the other three dicaffeoylquinic acids (1, 2, 4) and indomethacin in reduction of TNF-a and IL-1b concentrations (8.44 ± 0.62 and 5.83 ± 0.57 pg/mL compared to 12.60 ± 1.30 and 52.91 ± 5.20 pg/mL induced by indomethacin, respectively). ARTICLE HISTORY

No abstract

Sulphur compounds in sulphur rich food have been shown to significantly reduce the risk of cancer development. One such compound is sulforaphane (SF), a cancer chemopreventive agent identified in broccoli (F. cruciferae). In this study, SF content was assessed in extracts of several crucifer vegetables including broccoli, brussels sprout, green cabbage, red cabbage, Chinese kale and turnip, in parallel with anticancer and antioxidant activity. Among tested crucifers, cabbage demonstrated a pronounced anticancer effect against A-549 lung cancer cells, with an IC 50 value of 38 lg mL À1 , and correlated with high SF levels at 540 lg g À1 . Except for red cabbage and kale, crucifer extracts displayed moderate to weak activity in scavenging 2,2-diphenyl-1-picrylhydrazyl (DDPH) free radicals relative to vitamin E standard.