ABSTRACT
Among the herbal ingredients of HangAmDan-B, a medicinal formula that redirects macrophages to become tumoricidal effectors, we found that Panax notoginseng (Burk.) F. H. Chen is the active component responsible for its macrophage-mediated antitumor activity. The water extracted roots of P. notoginseng (PN) did not affect the viability of RAW264.7 murine macrophage-like cells and murine Lewis lung carcinoma (LLC) cells up to a concentration of 100[Formula: see text][Formula: see text]g/mL. However, the transfer of culture media from PN-treated RAW264.7 cells suppressed the growth of LLC cells. The expression of classically activated (M1) markers, such as interleukin (IL)-1[Formula: see text], monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-[Formula: see text], and inducible nitric oxide synthase (iNOS), was increased by PN treatment. The expression of alternatively activated (M2) markers including CD206, IL-10, and [Formula: see text]-[Formula: see text]-acetylhexosaminidases (YM-1) was reduced by PN treatment in the presence of IL-4. Flow cytometry also revealed that PN drives M1 activation of RAW264.7 cells. The transfer of culture media from PN-treated RAW264.7 cells induced the apoptosis of LLC cells as measured by flow cytometry using Annexin-V staining and western blot analysis for caspase cascade-related proteins. In addition, the results from in vivo tumor allograft model demonstrated that PN reduced both tumor volume and weight. The activation of macrophages toward an M1 phenotype was confirmed in the tumor allograft tumor model. These results collectively show that PN can serve as a potent anticancer agent through reeducation of macrophages toward an M1 phenotype.
Subject(s)
Antineoplastic Agents, Phytogenic , Carcinoma, Lewis Lung/pathology , Macrophage Activation/drug effects , Panax notoginseng/chemistry , Plant Extracts/pharmacology , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Survival/drug effects , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Dose-Response Relationship, Drug , Gene Expression/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/isolation & purification , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND AND OBJECTIVES: The failure of ST-segment resolution (STR) after primary percutaneous coronary intervention (pPCI) is associated with adverse clinical outcomes. However, the clinical predictors on admission for incomplete STR are poorly known. SUBJECTS AND METHODS: Patients undergoing pPCI (n=101, 79 males and 22 females, mean age 60.0 years) were divided into complete STR group (>/=70%, n=58) and incomplete STR group (<70%, n=43). The groups were compared according to clinical factors including history, electrocardiographic (ECG) patterns, angiographic features and laboratory data. RESULTS: The incomplete STR group contained more frequent hypertensive patients (p=0.04) and patients displaying longer tendency in total chest pain duration (p=0.08). This group was associated with worse clinical factors such as low ejection fraction (p=0.06), higher Killip class (p=0.08) and more death (p=0.042). Grade 3 ischemia pattern of ECG and precordial ST elevation (i,e anterior myocardial infarction) at admission were more frequent in the incomplete STR group (p=0.001 and 0.002, respectively). Initial troponin I, creatinin kinase -MB and brain natriuretic peptide levels were higher in the incomplete STR group (p=0.001, 0.002, and 0.043, respectively). Coronary angiography showed that culprit lesions were more frequent in left anterior descending artery than other arteries in the incomplete STR group of patients (p=0.002). Thrombolysis In Myocardial Infarction (TIMI) flow grades 2 or less before PCI was more frequent in the incomplete STR group (p=0.029). However, TIMI flow grade after PCI was not appreciably different between the two groups. Logistic regression analysis demonstrated that TIMI flow grade 2 or less was most powerful predictor for incomplete STR {odds ratio (OR)=12.12, 95% confidence interval (CI) 1.23-119.35, p=0.032}. Other independent predictors were anterior infarction (OR=3.39, CI 1.46-10.57, p=0.007), ischemia grade 3 ECG at admission (OR=3.87, CI 1.31-11.41, p=0.014), and hypertensive patients (OR=3.03, CI 1.13-8.15, p=0.027). CONCLUSION: Incomplete STR after pPCI is associated with poor prognostic clinical factors. TIMI flow grade 2 or less before pPCI, ST elevation on precordial leads, ischemia grade 3 pattern of initial ECG, and hypertensive patients are independent predictors for incomplete STR in the early stage.