β-mangostin suppresses LA-7 cells proliferation in vitro and in vivo: involvement of antioxidant enzyme modulation; suppression of matrix metalloproteinase and α6β4 integrin signalling pathways

β-mangostin (βM) was isolated from Cratoxylum arborescens to investigate anti-breast cancer effect in vitro and in vivo. βM exhibited an inhibitory effect on the growth of LA-7 cells in vitro with apoptosis formation. In the animal model, βM treatment was found to be effective in improving the tissue antioxidant enzymes such as superoxide dismutase and catalase activity (P < 0.05). βM treatment clearly exhibited apoptosis in mammary tumour tissues, and it was associated with regulation of PCNA and p53. The cDNA microarray gene expression followed by qRT-PCR based validation demonstrated that βM could mediate tumour reduction and prevent metastasis by reduction of MMP-9, MMP-13, and MMP-27. Moreover, the reduction of both 14-3-3β and ITGB4 genes indicated the involvement of α6β4 integrin signalling pathway. These findings showed that β-mangostin is a promising compound candidate as an anti-tumour agent against breast cancer

β-Mangostin induces p53-dependent G2/M cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway and NfkB suppression in MCF-7 cells

β-Mangostin (βM) was isolated from Cratoxylum arborescens to investigate its anti-cancer effect in MCF-7 cells. βM induced apoptosis by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of caspase-9 and -7 and consequently cleaved PARP leading to apoptotic was observed upon treatment. Reduction of both bid and caspase 8 and the up regulation of Fas showed the involvement of the extrinsic pathway. Significantly up regulated GADD45A and HRK genes were observed upon treatment, with concomitant inhibition of NF-kB to nucleus. The protein array had demonstrated the expression of HSP 70, HSP 60, XIAP, Survivin, p53 and Bax. Moreover, βM had showed p53-dependent G2/M cell cycle arrest by down regulation of cdc2 and PCNA. Together, the results demonstrated that the βM induced anti-proliferative effect, leading to G2/M phase cell cycle arrest and apoptosis through both the extrinsic and mitochondrial pathways with the involvement of the multiple pro and anti-apoptosis and NF-kB signalling pathways

Evaluation of Corn Genotypes for Resistance to Sesamia inferens

Corn, as the second most important cereal cultivated in Afghanistan, is subjected to numerous biotic and abiotic stresses limiting its productivity.&nbsp;Sesamia inferens&nbsp;is a polyphagous pest attacking this crop that causes severe damage and yield losses in Afghanistan. This study was conducted to evaluate the resistance to attack by&nbsp;Sesamia inferens&nbsp;of different corn landraces collected from different provinces of Afghanistan along with commercial hybrids. Evaluations for agronomical performance and resistance were done in two years under natural infestation with&nbsp;S. inferens.&nbsp;Differences among genotypes were significant for all traits. The landraces BU1, BU2, BU3&nbsp;showed to be a good source of stem resistance, and the landrace BU5considered to be a suitable material to improve yield in further breeding programs. This is a preliminary evaluation and the resistance of these landraces should be corroborated under artificial infestation because earlier genotypes could get the silking stage before the occurrence of the peak of insect infestation. &nbsp

Evaluation of Corn Genotypes for Resistance to Sesamia inferens

Corn, as the second most important cereal cultivated in Afghanistan, is subjected to numerous biotic and abiotic stresses limiting its productivity.&nbsp;Sesamia inferens&nbsp;is a polyphagous pest attacking this crop that causes severe damage and yield losses in Afghanistan. This study was conducted to evaluate the resistance to attack by&nbsp;Sesamia inferens&nbsp;of different corn landraces collected from different provinces of Afghanistan along with commercial hybrids. Evaluations for agronomical performance and resistance were done in two years under natural infestation with&nbsp;S. inferens.&nbsp;Differences among genotypes were significant for all traits. The landraces BU1, BU2, BU3&nbsp;showed to be a good source of stem resistance, and the landrace BU5considered to be a suitable material to improve yield in further breeding programs. This is a preliminary evaluation and the resistance of these landraces should be corroborated under artificial infestation because earlier genotypes could get the silking stage before the occurrence of the peak of insect infestation. &nbsp

Meta-analysis of seed weight QTLome using a consensus and highly dense genetic map in Brassica napus L

International audienceWe report here the discovery of high-confidence MQTL regions and of putative candidate genes associated with seed weight in B. napus using a highly dense consensus genetic map and by comparing various large-scale multiomics datasets. Seed weight (SW) is a direct determinant of seed yield in Brassica napus and is controlled by many loci. To unravel the main genomic regions associated with this complex trait, we used 13 available genetic maps to construct a consensus and highly dense map, comprising 40,401 polymorphic markers and 9191 genetic bins, harboring a cumulative length of 3047.8 cM. Then, we performed a meta-analysis using 639 projected SW quantitative trait loci (QTLs) obtained from studies conducted since 1999, enabling the identification of 57 meta-QTLS (MQTLs). The confidence intervals of our MQTLs were 9.8 and 4.3 times lower than the average CIs of the original QTLs for the A and C subgenomes, respectively, resulting in the detection of some key genes and several putative novel candidate genes associated with SW. By comparing the genes identified in MQTL intervals with multiomics datasets and coexpression analyses of common genes, we defined a more reliable and shorter list of putative candidate genes potentially involved in the regulation of seed maturation and SW. As an example, we provide a list of promising genes with high expression levels in seeds and embryos (e.g., BnaA03g04230D, BnaC03g08840D, BnaA10g29580D and BnaA03g27410D) that can be more finely studied through functional genetics experiments or that may be useful for MQTL-assisted breeding for SW. The high-density genetic consensus map and the single nucleotide polymorphism (SNP) physical map generated from the latest B. napus cv. Darmor-bzh v10 assembly will be a valuable resource for further mapping and map-based cloning of other important traits

alpha-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-kappa B and Hsp70 protein modulation in vitro, and tumor reduction in vivo

Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 µg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cance