Rose (Rosa gallica) Petal Extract Suppress Proliferation, Migration, and Invasion of Human Lung Adenocarcinoma A549 Cells through via the EGFR Signaling Pathway.

We sought to investigate the effect of rose petal extract (RPE) on the proliferation, migration, and invasion of cancer cells. RPE significantly inhibited the growth of lung and colorectal cancer cell lines, with rapid suppression of A549 lung cancer cells at low concentrations. These effects occurred concomitantly with downregulation of the cell proliferation mediators PCNA, cyclin D1, and c-myc. In addition, RPE suppressed the migration and invasion of A549 cells by inhibiting the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and -9). We hypothesize that the suppressive activity of RPE against lung cancer cell proliferation and early metastasis occurs via the EGFR-MAPK and mTOR-Akt signaling pathways. These early results highlight the significant potency of RPE, particularly for lung cancer cells, and warrant further investigation.

Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor.

Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell growth. Haspin kinase was identified as a direct target protein of coumestrol using kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We observed haspin kinase overexpression as well as greater phosphorylation of histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells. Computer modeling using the Schrödinger Suite program identified the binding interface within the ATP binding site. These findings suggest that the anti-cancer effect of coumestrol is due to the direct targeting of haspin kinase. Coumestrol has considerable potential for further development as a novel anti-cancer agent.

PKA negatively regulates PP2Cß to activate NF-κB-mediated inflammatory signaling.

Protein phosphatase 2Cß (PP2Cß) was found to act as a negative regulator of NF-κB-mediated inflammatory signaling; however, its regulatory mechanism has not been examined. Here, we show that protein kinase A (PKA) phosphorylates the PP2Cß, which was inhibited by PKA-specific inhibitor, H89. Mutation analysis of serine residues in PP2Cß revealed that Ser-195 in PP2Cß is phosphorylated by PKA. Importantly, PKA inhibition by H89 abrogated the Forskolin-induced destabilization of PP2Cß against ubiquitin-dependent proteosomal degradation pathway. Furthermore, H89 treatment efficiently reversed the negative effect of Forskolin on the anti-inflammatory function of PP2Cß. Collectively, these data suggest that PKA destabilizes PP2Cß upon inflammatory stimuli via phosphorylation of Ser-195 in PP2Cß.

The chalcone derivative Chana 1 protects against amyloid ß peptide-induced oxidative stress and cognitive impairment.

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid ß (Aß)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aß-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aß-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aß-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

Difference between proximal and distal microsatellite-unstable sporadic colorectal cancers: analysis of clinicopathological and molecular features and prognoses.

BACKGROUND: Distal microsatellite instability (MSI)-high colorectal cancers (CRCs) have been investigated by few studies and are generally regarded as having similar features to proximal MSI-high CRCs. In the present study, we aimed to elucidate whether distal sporadic MSI-high CRCs displayed distinguished clinicopathological and molecular features from proximal MSI-high CRCs. METHODS: All patients who underwent their first surgical resections for stage I-IV sporadic CRCs between August 2003 and August 2006 were initially considered for enrollment, and their MSI data were prospectively collected. Among them, 135 patients with MSI-high CRCs (86 proximal and 49 distal CRCs) were finally identified. The clinicopathological and molecular characteristics, and prognosis of these cases with MSI-high CRCs were reviewed and compared according to tumor site (proximal versus distal). RESULTS: Distal MSI-high CRCs showed significantly more frequent association with younger age, male gender, differentiated histology, small tumor size, distant metastasis, stability in BAT25 and BAT26, and hMLH1 expression on immunohistochemical staining as compared with proximal MSI-high CRCs. In addition, distal MSI-high CRCs demonstrated significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (87.0% versus 97.4%; 81.6% versus 95.9%). For stage III-IV CRCs, distal MSI-high CRCs also showed significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (72.2% vs. 90.5%; 58.3% vs. 94.4%). CONCLUSIONS: These results indicated that distal sporadic MSI-high CRCs formed a distinct subgroup with distinguished clinicopathological and molecular features from proximal MSI-high CRCs. In addition, this study demonstrated that distal MSI-high CRCs had worse prognosis than proximal MSI-high CRCs.

Differential diagnosis for intrahepatic biliary cystadenoma and hepatic simple cyst: significance of cystic fluid analysis and radiologic findings.

GOALS: This study evaluated the significance of cystic fluid analysis and radiologic findings in the differential diagnosis of biliary cystadenomas (BCA) and hepatic simple cysts (HSCs). BACKGROUND: BCA are premalignant lesions. The treatment of choice is surgical excision. It is important to differentiate BCA from HSCs because they have different clinical significances and treatment plans. However, it is difficult to preoperatively differentiate a BCA from a HSC. STUDY: This retrospective study was done with 31 patients suffering from pathologically diagnosed BCA or HSC. All patients underwent surgery between May 1995 and June 2008 at a single institution and had cystic fluid analysis preoperatively or intraoperatively. RESULTS: We discovered no statistically significant differences in cystic fluid carbohydrate antigen 19-9 (CA 19-9) levels or carcinoembryonic antigen levels when comparing BCA (n=17) and HSCs (n=14). BCA were significantly more frequently associated with female sex (17/17 vs. 10/14, P=0.032), presence of a septum (16/17 vs.5/14, P=0.001), and septal thickening (8/17 vs. 1/14, P=0.021). All 3 cases with calcifications belonged to the BCA group, but sample size was too small to demonstrate statistical significance. There were no statistically significant differences in other clinical and radiologic findings including age, presence of symptoms, serum tumor markers, serum chemistry, size, location, lobulation, septal enhancement, wall enhancement, wall thickening, mural nodule, or biliary dilatation. CONCLUSIONS: Cystic fluid carbohydrate antigen 19-9 levels and carcinoembryonic antigen levels were not useful for differential diagnosis of BCA vs. HSC. BCA were more common than HSCs in females, patients with a septum, and patients with septal thickening.

Sporadic colorectal carcinomas with low-level microsatellite instability in Korea: do they form a distinct subgroup with distinguished clinicopathological features?

BACKGROUND: The biologic significance of low-level microsatellite instability (MSI) in colorectal cancers (CRCs) remains unclear. This study aimed to elucidate whether sporadic MSI-low CRCs in Korea displayed distinguished clinicopathological characteristics from microsatellite stable (MSS) and MSI-high CRCs. METHODS: We consecutively enrolled 657 patients who underwent their first surgical resections for stage I-IV sporadic CRCs and compared their clinicopathological features and prognosis after resection according to MSI status (574 MSS, 30 MSI-low and 53 MSI-high CRCs). RESULTS: When compared with MSS CRCs, MSI-low CRCs showed significantly more frequent association with poorly differentiated histology, mucinous carcinoma, and large tumour size. In addition, MSI-low CRCs demonstrated significantly less frequent lymph node metastasis and advanced tumour stage than MSS CRCs. When compared with MSI-high CRCs, MSI-low CRCs were significantly more frequently located in distal colon. Three-year overall and disease-free survival rates of MSS, MSI-low and MSI-high CRCs were 83.5%, 90.0% and 91.7% and 82.0%, 89.1% and 87.5%, respectively and neither demonstrated significant difference between three groups. CONCLUSIONS: These results indicated that sporadic MSI-low CRCs in Korea displayed distinguished clinicopathological features and might form a distinct subgroup especially from MSS CRCs. Further large studies are required to evaluate the impact of MSI-low status on prognosis.