Human liposarcoma is the most common soft tissue sarcoma. There is no effective therapy so far except for surgery. In this study, we report for the first time that curcumin induces endoplasmic reticulum (ER) stress in human liposarcoma cells via interacting with sarcoplasmic/endoplasmic reticulum Ca 2þ -ATPase 2 (SERCA2). Curcumin dose-dependently inhibited the cell survival of human liposarcoma cell line SW872 cells, but did not affect that of human normal adipose-derived cells. Curcumin-mediated ER stress via inhibiting the activity of SERCA2 caused increasing expressions of CHOP and its transcription target death receptor 5 (TRAIL-R2), leading to a caspase-3 and caspase-8 cascade-dependent apoptosis in SW872 cells in vitro and in vivo. Moreover, 70% of human liposarcoma tissues showed an elevated SERCA2 expression compared with normal adipose tissues. Curcumin dose-dependently inhibited the activity of SERCA2, and the interaction of molecular docking and colocalization in ER of curcumin with SERCA2 were further observed. These findings suggest that curcumin may serve as a potent agent for curing human liposarcoma via targeting SERCA2. Mol Cancer Ther; 10(3); 461-71. Ó2011 AACR.
Harpins of phytopathogenic bacteria stimulate defense and plant growth in many types of plants, conferring disease resistance and enhanced yield. In a previous study, we characterized nine fragments of the harpin protein HpaG(Xooc) from Xanthomonas oryzae pv. oryzicola for plant defense elicitation and plant growth stimulation activity relative to the intact protein. In plants grown under controlled conditions, the fragment HpaG10-42 was more active in both regards than HpaG(Xooc). Here, we demonstrate that the activity of HpaG10-42 in rice under field conditions significantly exceeds that of HpaG(Xooc), stimulating resistance to three important diseases and increasing grain yield. We carried out tests in 672 experimental plots with nine cultivars of rice planted at three locations. Application protocols were optimized by testing variations in application rate, frequency, and timing with respect to rice growth stage. Of the concentrations (24, 24, 12, and 6 microg/ml), and number and timing of applications (at one to four different stages of growth) tested, HpaG10-42 at 6 microg/ml applied to plants once at nursery seedling stage and three times in the field was most effective. Bacterial blight, rice blast, and sheath blight were reduced 61.6 and 56.4, 93.6 and 76.0, and 93.2 and 55.0% in indica and japonica cultivars, respectively, relative to controls. Grain yields were 22 to 27% greater. These results are similar to results obtained with typical local management practices, including use of chemicals, to decrease disease severities and increase yield in rice. Our results demonstrate that the HpaG10-42 protein fragment can be used effectively to control diseases and increase yield of this staple food crop.
Bacterial blight (BB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo) is a common, widespread, and highly devastating disease that affects rice yield. Breeding resistant cultivars is considered the most effective measure for controlling this disease. The introgression line G252 derived from Yuanjiang common wild rice (Oryza rufipogon) was highly resistant to all tested Xoo strains, including C5, C9, PXO99, PB, T7147Y8, Hzhj19, YM1, YM187, YJdp-2, and YJws-2. To identify the BB resistance gene(s) of G252, we developed an F2 population from the cross between G252 and 02428. A linkage analysis was carried out between the phenotype and genotype in the population. A segregation ratio of 3:1 was observed between the resistant and susceptible individuals in F2 progeny, indicating a dominant resistance gene, Xa47(t), in G252. The resistance gene was mapped within an approximately 26.24 kb physical region on chromosome 11 between two InDel markers, R13I14 and 13rbq-71; and moreover, one InDel marker, Hxjy-1, co-segregated with Xa47(t). Three genes were predicted within the target region, including a promising candidate gene encoding a nucleotide-binding domain and leucine-rich repeat (NLR) protein (LOC_Os11g46200) by combining the structure and expression analysis. Physical mapping data suggested that Xa47(t) was a new broad-spectrum BB resistance gene.
The relapse and resistance to chemo-and radiotherapy are main problems in the treatment of human liposarcoma. It is important to find a functional marker existing in the liposarcoma cells for targeting. In this article, we established a new sub-cell line SW872-S cells with high tumorigenicity from human liposarcoma SW872 cells by repeated inoculation approach. The characteristic of the sub-cell line is linked to the high levels of integrin a6 on the surface. The integrin a6 high cells show much higher tumor initiation and self-renewal potential in vivo than integrin a6 low cells do. Targeting integrin a6 with its specific short interfering RNA and antibody significantly inhibits the cell adhesion to laminin and the tumor growth in vitro and in vivo, respectively. Interestingly, integrin a6 marks almost all of the surgical biopsy specimens of patients with liposarcoma relapse. Moreover, integrin a6 is found to coexpress with CD13, which might contribute to the antiapoptosis ability of integrin a6 high cells. Consistently, integrin a6 high cells are more sensitive to the CD13 inhibitor bestatin, and 61% of 23 other human tumor cell lines also contain integrin a6 high CD13 high subgroup.These results provide evidence, for the first time, to our knowledge, that integrin a6 and CD13 can serve as functional markers of the tumor-initiation subcell population in human liposarcoma as well as other cancers for therapeutic targeting. Mol Cancer Ther; 10(12); 2276-86. Ó2011 AACR.
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