Acanthopanax senticosus: Photochemistry and Anticancer Potential.

Acanthopanax senticosus (previously classified as Eleutherococcus senticosus), commonly known as Ciwujia or Siberian Ginseng, is a traditional Chinese medicine (TCM), widely used for its high medicinal value, such as antifatigue, anti-inflammation, antistress, anti-ulcer and cardiovascular functions, in China, Korea, Japan and Russia. In the past decades, researchers worldwide have conducted systematic investigations on this herb, from chemistry to pharmacology, and a large number of chemical components have been characterized for their significant pharmacological effects. However, reports about the anticancer effects of this plant had been rare until recently, when considerable pharmacological experiments both in vitro and in vivo were conducted to study the anticancer effects of this herb. A. senticosus has been found to have inhibitory effects on malignant tumors, such as those in the lung and liver, suggesting that A. senticosus has potential to be developed as an effective anticancer drug. This paper reviews recent findings on the pharmacological properties of A. senticosus, with a focus on its anticancer effects.

SOX7 co-regulates Wnt/ß-catenin signaling with Axin-2: both expressed at low levels in breast cancer.

SOX7 as a tumor suppressor belongs to the SOX F gene subfamily and is associated with a variety of human cancers, including breast cancer, but the mechanisms involved are largely unclear. In the current study, we investigated the interactions between SOX7 and AXIN2 in their co-regulation on the Wnt/ß-catenin signal pathway, using clinical specimens and microarray gene expression data from the GEO database, for their roles in breast cancer. We compared the expression levels of SOX7 and other co-expressed genes in the Wnt/ß-catenin pathway and found that the expression of SOX7, SOX17 and SOX18 was all reduced significantly in the breast cancer tissues compared to normal controls. AXIN2 had the highest co-relativity with SOX7 in the Wnt/ß-catenin signaling pathway. Clinicopathological analysis demonstrated that the down-regulated SOX7 was significantly correlated with advanced stages and poorly differentiated breast cancers. Consistent with bioinformatics predictions, SOX7 was correlated positively with AXIN2 and negatively with ß-catenin, suggesting that SOX7 and AXIN2 might play important roles as co-regulators through the Wnt-ß-catenin pathway in the breast tissue to affect the carcinogenesis process. Our results also showed Smad7 as the target of SOX7 and AXIN2 in controlling breast cancer progression through the Wnt/ß-catenin signaling pathway.

Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/ß-catenin signaling pathway.

BACKGROUND: Products of the SOX gene family play important roles in the life process. One of the members, SOX7, is associated with the development of a variety of cancers as a tumor suppression factor, but its relevance with ovarian cancer was unclear. In this study, we investigated the involvement of SOX7 in the progression and prognosis of epithelial ovarian cancer (EOC) and the involved mechanisms. METHODS: Expression profiles in two independent microarray data sets were analyzed for SOX7 between malignant and normal tissues. The expression levels of SOX7 in EOC, borderline ovarian tumors and normal ovarian tissues were measured by immunohistochemistry. We also measured levels of COX2 and cyclin-D1 to examine their possible involvement in the same signal transduction pathway as SOX7. RESULTS: The expression of SOX7 was significantly reduced in ovarian cancer tissues compared with normal controls, strongly indicating that SOX7 might be a negative regulator in the Wnt/ß-catenin pathway in ovarian cancer. By immunohistochemistry staining, the protein expression of SOX7 showed a consistent trend with that of the gene expression microarray analysis. By contrast, the protein expression level of COX2 and cyclin-D1 increased as the tumor malignancy progressed, suggesting that SOX7 may function through the Wnt/ß-catenin signaling pathway as a tumor suppressor. In comparison between the protein expression levels of SOX7 with pathological features of the cancer, we found that SOX7 was down-regulated mainly in serous cystadenocarcinoma and advanced stages of the cancers. CONCLUSIONS: The expression of SOX7 correlates with tumor progression as a tumor suppressor, possibly through the Wnt/ß-catenin signaling pathway in ovarian cancers, suggesting that SOX7 may be a promising prognostic marker.

Design, synthesis, and fungicidal activity of novel carboxylic acid amides represented by N-benzhydryl valinamode carbamates.

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 µg mL(-1).

Expression of renin-angiotensin system and peroxisome proliferator-activated receptors in alcoholic cardiomyopathy.

BACKGROUND: Alcoholic cardiomyopathy (ACM) develops in response to chronic alcohol intake and it is hypothesized that activation of the renin-angiotensin system (RAS) and disorders in energy metabolism may play important roles in its onset. Given that the expression of peroxisome proliferator-activated receptors (PPARalpha and PPARgamma) changes with alterations in cardiac metabolism and myocardial remodeling, this study was designed to test the hypothesis that protein expression of PPARalpha and PPARgamma is correlated with RAS activation in ACM. METHODS: For the first experiment, rats were divided into 3 groups: 30 received alcohol (intragastric administration with ad libitum drinking), 30 received alcohol and irbesartan (5 mg/kg/d, p.o.), and 30 served as controls. RAS activity and protein expression of PPARalpha and PPARgamma were evaluated in rats following 6 months of alcohol feeding using radioimmunoassay, reverse transcriptase PCR, and Western blot methods. For the second experiment, rats were divided into 4 groups: 10 rats received alcohol/irbesartan (5 mg/kg/d, p.o.)/PD98059 (methyl ethyl ketone [MEK]-1 inhibitor) (0.3 mg/kg/d, p.o.), 10 rats received alcohol/PD98059, 10 rats received alcohol/irbesartan, and 10 rats received alcohol alone. Myocardial PPARalpha and PPARgamma protein expression was detected following 6 months of alcohol feeding using Western blot method. RESULTS: Compared with controls, myocardial angiotensin (Ang) I, Ang II, and renin levels were progressively increased at 2, 4, and 6 months of alcohol intake. mRNA expression of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and AT1 was increased at 6 months. Moreover, activated RAS downregulated PPARalpha and upregulated PPARgamma protein expression as ACM progressed. Finally, extracellular signal regulated kinase 1 and 2 (ERK1/2) was shown to play a key role in the regulation of protein expression of PPARalpha and PPARgamma. CONCLUSION: These results suggest that RAS is activated during the development of ACM. Moreover, ERK1/2 plays a key role in the regulation of protein expression of PPARalpha and PPARgamma by RAS in ACM.

[The experimental study on changes of endothelial nitric oxide synthase and plasminogen activator inhibitor-1 protein in the canine atrial fibrillation model].

OBJECTIVE: To evaluate the changes in the expressions of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) and the alterations of nitric oxide (NO) concentration in atrial endocardium in atrial fibrillation (AF) in order to investigate the mechanisms that contribute to thrombosis. METHODS: In canine AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas the controls had no atrial pacing. NO production was measured by NO-specific microelectrode. The expression of endocardial eNOS and PAI-1 protein were determined by Western blot analysis and immunohistochemical Staining. Plasma levels of PAI-1 were analysed by Enzyme-linked immunoadsorbent assay. RESULTS: Left atrial NO concentration was decreased in AF than that in controls [(23.4 +/- 5.8)nmol/L vs (63.8 +/- 16.1)nmol/L, P < 0.01]. Endocardial eNOS expression was also significantly decreased (855 +/- 217 vs 2320 +/- 694, P < 0.05), whereas the expression of the PAI-1 was increased (3164 +/- 827 vs 1371 +/- 352, P < 0.01). Neither NO concentration, nor PAI-1, eNOS expression were altered in the right atria at the same time. A significant increase for plasma levels of PAI-1 was also detected in AF group. No correlation was found between eNOS and PAI-1 protein expression (r = 0.217, P > 0.05). CONCLUSION: In the canine model AF was associated with a marked decrease in endocardial NOS expression and NO concentration and with an increase in PAI-1 expression in the left atrium, which may contribute to the thrombosis in AF.