Adiponectin inhibits oxidative stress in human prostate carcinoma cells

Abstract

BACKGROUND: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case-control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals. METHODS:Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro-Wilk test and results were analyzed using a one-way analysis of variance. RESULTS:We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an overall anti-oxidative effect, as the total anti-oxidative potential, catalase activity and protein levels, and manganese superoxide dismutase protein levels increased significantly (Po0.05) in both cell lines after treatment with adiponectin.CONCLUSION: Lower levels of adiponectin in obese individuals may result in higher levels of prostatic OS, which may explain the clinical association between obesity, hypoadiponectinemia and PC.

Underexpression of tumour suppressor LKB1 in clear cell renal cell carcinoma is common and confers growth advantage in vitro and in vivo

“…Human ccRCC 786-O cells stably expressing shRNA specific to LKB1 (shLKB1) demonstrated a 47% knockdown of LKB1 protein expression compared with 786-O cells stably expressing noneffective scrambled control shRNA (shControl) (Figure 3A). Furthermore, when increasing concentrations of adiponectin, a known activator of AMPK (Lu et al , 2012), were used to treat cells, we demonstrate that the activation of AMPK was virtually abolished in shLKB1 cells when compared with shControl cells. The rate of proliferation was also significantly higher in shLKB1 cells than in shControl cells (Figure 3B).…”

Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation

“…In fact, it has been shown that the reduced concentrations of adiponectin observed in obesity may represent one of the mechanisms that connect obesity with the development and progression of cancer 83-86. importantly, adiponectin levels are decreased in obesity-associated insulin resistance and cancer 87. Insulin resistance is increased, with resultant elevation in insulin and bioavalible IGF1 levels, which enhance tumor cellular proliferation 88,89.…”

Role of adiponectin in adipose tissue wound healing

“…For example, adiponectin was used to treat damage resulting from alcoholic liver disease (Ouchi et al, 2011) and ethanol-induced gastric mucosal injury (Xu et al, 2003). In addition, adiponectin-mediated repair of periodontal damage (Yamamoto et al, 2012) and hearing loss has been demonstrated, and it plays important roles in prostate cancer (Salathia et al, 2013) and colon carcinoma (Lu et al, 2012).…”