Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RLIP76 is known to play a role in cell growth, division, apoptosis, and chemosensitivity in various malignant cancer cells. However, few studies have been done on the role of RLIP76 in leukemia. In this study, human leukemia cell line U937 was transiently transfected with a RLIP76-targeted short hairpin RNA (shRNA) to investigate the effects of RLIP76 on cellular functions. Real-time PCR and western blot analysis revealed that the expression levels of RLIP76 mRNA and protein in U937 cells were significantly suppressed after transfection with shRNA-containing vector. Knockdown of RLIP76 significantly inhibited cell growth and decreased the colony formation rate, as assessed by trypan blue exclusion and colony formation assay. Flow cytometry analysis showed that reduced RLIP76 expression resulted in cell cycle arrest at G1 phase and induced apoptosis. Meanwhile, western blot analysis demonstrated that RLIP76 knockdown increased expression of Bax, cleaved caspase-3/-9, and cleaved poly (ADP-ribose) polymerase (PARP) but reduced the expression of cyclin D1, cyclin E, and Bcl-2 in U937 cells. Finally, knockdown of RLIP76 in U937 cells also enhanced their chemosensitivity to daunorubicin. Taken together, this study suggests that RLIP76 is a potential target for developing novel therapeutic strategies for leukemia.
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PMID:Knockdown of RLIP76 expression by RNA interference inhibits proliferation, enhances apoptosis, and increases chemosensitivity to daunorubicin in U937 leukemia cells. 2483 8

Consumption of citrus-fruits is associated with reduced incidence of breast cancer (BC), the most common cancer diagnosed in women across the globe. In this study, we investigated the anticancer potential of 2-Hydroxyflavanone (2HF) in BC. 2HF, a citrus-bioflavonoid, has demonstrated anticancer properties in various cancers, but its anticancer role in BC has not been well studied. We investigated the in vitro and in vivo growth inhibitory effects of 2HF in an array of BC lines and in xenograft mouse models of ER-positive and HER2-positive BC cells. Compared to control, 2HF treatment reduced cell viability and suppressed migratory and invasive potential of BC cells, while, no growth inhibitory effects were observed in non-tumorigenic breast epithelial cells. Further, 2HF inhibited the expression of RLIP76, a stress-defensive and anti-apoptotic protein, which is over-expressed in BC cells and simultaneously reduced proliferation of BC cells. Nude mice bearing MCF7 or SKBR3 BC cells xenografts treated with either 2HF or targeting RLIP76 by RLIP76-antisense or RLIP76-antibody treatment had significantly lower tumor-weight as compared to corresponding controls. In addition, Western-blotting and immunohistochemical analysis of tumor tissue from control and treatment group mice showed that 2HF decreased protein expression levels of RLIP76, and the decrease was similar to those seen following RLIP76-antisense treatment. Furthermore, 2HF decreased expression of Ki67, CD31, vimentin, inhibited phosphorylation of Akt and expression of survivin and Bcl2, and increased levels of Bax, E-cadherin, and cleaved-PARP. Therefore, our results indicate that 2HF may suppress BC growth in vitro and in vivo by targeting RLIP76, and may serve as a potential adjuvant treatment in BC patients.
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PMID:2'-Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76. 3013 44