Anti-Tumor Study Of Scopoletin And Rubbing-Mercapto-Nitrile From Nicotiana Glauca

Nicotiana glauca (Solanaceae) telah digunakan secara tradisional untuk merawat jangkitan dan kanser. Tumbuhan ini dilaporkan kaya dengan komponen–komponen yang baik untuk kesihatan. Dalam kajian ini, dua komponen anti-tumor daripada ekstrak n-heksana N. glauca telah berjaya diasingkan, iaitu scopoletin dan satu komponen baru, Rubbing-Mercapto-Nitrile (RMN). Pengasingan scopoletin berpandukan aktiviti anti-angiogenesis telah dijalankan menggunakan ekstrak daripada batang N. glauca. Aktiviti anti-angiogenesis scopoletin dikaji menggunakan model–model angiogenesis secara ex vivo dan in vivo. Keberkesanan anti-tumorigenik scopoletin dikaji menggunakan xenograf tumor kolorektal manusia pada mencit nude atimik. Scopoletin menyebabkan perencatan signifikan dalam percambahan salur mikro pada eksplan aortik tikus dengan nilai kepekatan perencatan 50% adalah 34 μg/ml. Scopoletin (100 dan 200 mg/kg) merencat dengan berkesan vaskularisasi plak matrigel yang diimplan pada mencit nude, masing–masing sebanyak 59.72% dan 89.4%. Nicotiana glauca (Solanaceae) has been traditionally used as a folk remedy to treat infections and cancer. It has been reported as a rich source of beneficial phytochemicals. In the present study, two anti-tumor compounds derived from n-hexane extract of N. glauca namely scopoletin and, a novel compound, Rubbing-Mercapto-Nitrile (RMN) have been isolated. Antiangiogenesis-guided isolation of scopoletin was conducted using an extract from the stem of N. glauca. The anti-angiogenic activity of scopoletin was investigated using ex vivo and in vivo angiogenesis models. The antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenografts using athymic nude mice. Scopoletin caused significant suppression of microvessel sprouting in rat aortic explants with IC50 of 34 μg/ml. Scopoletin (100 and 200 mg/kg) strongly inhibited (59.72% and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans