Micropropagation and production of eurycomanone, 9- methoxycanthin-6-one and canthin-6-one in roots of Eurycoma longifolia plantlets

Eurycoma longifolia or Tongkat Ali is a well known medicinal plant in Malaysia. The plants are used as main portion in herbal preparation, and have been extensively harvested. Generally, most of the raw materials required by the industries are heavily collected from the natural forests, thereby resulting in the uncontrolled exploitation of the plant in the wild. Hence, there is a need to ensure adequate supply of quality E. longifolia for the use of the related industries and for conservation purposes. Micropropagation has proved to be an alternative for the multiplication of medicinal and aromatic plants and it can allow the future commercial use of E. longifolia in the herbal industries. In this study, E. longifolia plantlets were successfully mass-produced using axillary shoot multiplication techniques, and the production of eurycomanone, 9-methoxycanthin-6-one and canthin-6-one compounds of E. longifolia were detected in roots of tissue culture plantlets.Key words: E. longifolia, Tongkat Ali, micropropagation, eurycomanone, 9-methoxycanthin-6-one, canthin-6- one

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR=1.33, p=4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR=1.07, p=0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR=0.90, p=0.00033; rs927062, OR =0.94, p=0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations