coenzyme-q10 and Kidney-Neoplasms

P3H4, as a kind of quinone compounds, is a coenzyme Q10 (ubiquinone) analogues. A recent study investigated the role of P3H4 on cerebral ischemia-reperfusion and hypertension. It is well known that ischemia-reperfusion is closely associated with kidney disease. This study aims to investigate the impact of P3H4 in the occurrence and development of the tumor.. A total of 40 rats at 8-week old were selected to establish renal cancer model by burying suture method for 4 months. The rats in the experimental group received P3H4 treatment at 100 mg/kg every 48 h for consecutive 4 weeks, while the rats in control received normal saline. H&E staining was applied to test the histological changes of tissue at 0, 1, 2 weeks after treatment. Gene microarray was adopted to screen miRNA expression to explore the function of miRNA in renal cancer cell line. Renal cancer cell migration and invasion were evaluated by wound healing and transwell assays after the treatment of P3H4, miR-1a, miR-133a, respectively.. The rats were randomly equally divided into experimental group and control. HE staining result showed renal interstitial fibroblasts hyperplasia, renal tubular necrosis, and glomerular reduction after modeling. P3H4 treatment significantly alleviated the lesion severity and inhibited the tumor cells invasion. Microarray demonstrated that miR-1a and miR-133a were significantly upregulated in rat renal cancer tissue after the treatment of P3H4. The overexpression of miR-1a and miR-133a markedly reduced renal cell invasion and migration, which was consistent with the effect of P3H4.. P3H4 suppressed the development of renal carcinoma through upregulating miR-1a and miR-13a, which provides fundamental leads for the future anti-cancer therapy.

Topics: Animals; Cell Line, Tumor; Female; Kidney Neoplasms; Male; MicroRNAs; Random Allocation; Rats; Rats, Sprague-Dawley; Ubiquinone; Up-Regulation

Current studies of the TERE1 (UBIAD1) protein emphasize its multifactorial influence on the cell, in part due to its broad sub-cellular distribution to mitochondria, endoplasmic reticulum and golgi. However, the profound effects of TERE1 relate to its prenyltransferase activity for synthesis of the bioactive quinones menaquinone and COQ10. Menaquinone (aka, vitamin K-2) serves multiple roles: as a carrier in mitochondrial electron transport, as a ligand for SXR nuclear hormone receptor activation, as a redox modulator, and as an alkylator of cellular targets. We initially described the TERE1 (UBIAD1) protein as a tumor suppressor based upon reduced expression in urological cancer specimens and the inhibition of growth of tumor cell lines/xenografts upon ectopic expression. To extend this potential tumor suppressor role for the TERE1 protein to renal cell carcinoma (RCC), we applied TERE1 immunohistochemistry to a TMA panel of 28 RCC lesions and determined that in 57% of RCC lesions, TERE1 expression was reduced (36%) or absent (21%). Ectopic TERE1 expression caused an 80% decrease in growth of Caki-1 and Caki-2 cell lines, a significantly decreased colony formation, and increased caspase 3/7 activity in a panel of RCC cell lines. Furthermore, TERE1 expression increased mitochondrial oxygen consumption and hydrogen production, oxidative stress and NO production. Based on the elevated cholesterol and altered metabolic phenotype of RCC, we also examined the effects of TERE1 and the interacting protein TBL2 on cellular cholesterol. Ectopic TERE1 or TBL2 expression in Caki-1, Caki-2 and HEK 293 cells reduced cholesterol by up to 40%. RT-PCR analysis determined that TERE1 activated several SXR targets known to regulate lipid metabolism, consistent with predictions based on its role in menaquinone synthesis. Loss of TERE1 may contribute to the altered lipid metabolic phenotype associated with progression in RCC via an uncoupling of ROS/RNS and SXR signaling from apoptosis by elevation of cholesterol.

Topics: Apoptosis; Carcinoma, Renal Cell; Caspase 3; Caspase 7; Cell Line, Tumor; Cell Proliferation; Cholesterol; Dimethylallyltranstransferase; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Hydrogen; Kidney Neoplasms; Lipid Metabolism; Mitochondria; Nitric Oxide; Oxidative Stress; Oxygen; Pregnane X Receptor; Reactive Oxygen Species; Receptors, Steroid; Ubiquinone; Vitamin K 2

Topics: Chromatography, High Pressure Liquid; Coenzymes; Humans; Kidney; Kidney Neoplasms; Ubiquinone