ABSTRACT
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for the fourth leading cause of all cancer deaths. Scientific evidence has found that plant extracts seem to be a reliable choice due to their multitarget effects against HCC. Juniperus communis has been used for centuries in traditional medicine and its anticancer properties have been reported. As a result, the purpose of the study was to investigate the anticancer effect and mechanism of J. communis extract (JCo extract) on HCC in vitro and in vivo. In the present study, we found that JCo extract inhibited the growth of human HCC cells by inducing cell cycle arrest at the G0/G1 phase, extensive apoptosis and suppressing metastatic protein expressions in HCC cells. Moreover, the combinational treatment of JCo and VP-16 was found to enhance the anticancer effect, revealing that JCo extract might have the potential to be utilized as an adjuvant to promote HCC treatment. Furthermore, in vivo study, JCo extract significantly suppressed HCC tumor growth and extended the lifespan with no or low systemic and pathological toxicity. JCo extract significantly up-regulated the expression of pro-apoptotic proteins and tumor suppressor p53, suppressed VEGF/VEGFR autocrine signaling, down-regulated cell cycle regulatory proteins and MMP2/MMP9 proteins. Overall, our results provide a basis for exploiting JCo extract as a potential anticancer agent against HCC.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular/drug therapy , Juniperus , Liver Neoplasms/drug therapy , Plant Extracts/pharmacology , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Juniperus/chemistry , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Plant Extracts/isolation & purification , Signal Transduction , Xenograft Model Antitumor AssaysABSTRACT
Obesity is a public health problem that has raised concerns worldwide and is often associated with hepatic steatosis. Hepassocin is a novel hepatokine that causes hepatic steatosis and induces insulin resistance (IR). However, the role of hepassocin in obesity remains obscure. Thus, the aim of this study was to investigate the relationship between hepassocin levels and obesity. In total, 371 subjects who had a normal weight (NW), were overweight, or were obese were enrolled. We found that hepassocin levels in subjects who were overweight (6,705 ± 1,707 pg/ml) or obese (7,335 ± 2,077 pg/ml) were significantly higher than those of subjects with a NW (5,767 ± 1,500 pg/ml) (p < .001, test for trend). A multiple linear regression analysis showed that the body-mass index, waist circumference, nonalcoholic fatty liver disease, and homeostatic model assessment of IR were independently associated with hepassocin after adjusting for age, sex, high-sensitivity C-reactive protein, systolic blood pressure, high-density lipoprotein-cholesterol, log triglycerides, alanine transaminase, and the estimated glomerular filtration rate. This study provides evidence that subjects who were overweight or obese had significantly higher hepassocin levels than those with a NW. Hepassocin may be a useful biomarker in managing obesity and its related metabolic dysregulation.
