Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells

Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

Water Extracts of Anthriscus sylvestris Leaf induces Apoptosis in FaDu Human Hypopharynx Squamous Carcinoma Cells

Anthriscus sylvestris (L.) Hoffm. is a perennial herb found widely distributed in various regions of Korea, Europe, and New Zealand. The root of A. sylvestris have been extensively used in the treatment for antitussive, antipyretic, cough remedy in Oriental medicine, but the physiologically active function of the leaf of A. sylvestris is as yet unknown. In this study, we investigated the anti-cancer activity and the mechanism of cell death of water extracts of leaf of Anthriscus sylvestris (WELAS), on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that WELAS treatment inhibited cell viability in a concentration- and time-dependent manner. In addition, the treatment of WELAS markedly induced apoptosis in FaDu cells, as determined by the viability assay, DAPI stain and FACS analysis. WELAS also increased the proteolytic cleavage of procaspase-3, -9 and PARP (poly(ADP-ribose) polymerase). In addition, exposure to WELAS decreased the expression of Bcl-2 (an anti-apoptotic factor), but increased the expression of Bax (a pro-apoptotic factor), suggesting that mitochondria-dependent apoptotic pathways are mediated in WELAS-induced apoptosis. Taken together, these results indicate that water extracts of leaf of A. sylvestris inhibits cell growth and induces apoptosis via the mitochondrial-dependent apoptotic pathway in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, we propose that the water extracts of leaf of A. sylvestris is a novel chemotherapeutic drug, having growth inhibitory properties and induction of apoptosis in human oral cancer cells.

Simvastatin and Losartan Differentially and Synergistically Inhibit Atherosclerosis in Apolipoprotein E-/- Mice

BACKGROUND AND OBJECTIVES: Since statins and angiotensin receptor blockers are a frequently prescribed combination in patients with atherosclerotic cardiovascular diseases, we tested the interactive effects of simvastatin and losartan on atherosclerosis in apolipoprotein E (apoE)-/- mice. MATERIALS AND METHODS: Apolipoprotein E-/- mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks, with and without simvastatin (40 mg/kg) and/or losartan (20 mg/kg). The mice were divided into 5 groups and were fed as follows: regular chow (control diet, n=5), HFHC diet (n=6), HFHC diet with losartan (n=6), HFHC diet with simvastatin (n=6), and HFHC diet with both losartan and simvastatin (n=6). RESULTS: Losartan treatment in apoE-/- mice significantly decreased atherosclerotic lesion areas in whole aortic strips stained with Oil Red O. The plaque area measured at the aortic sinus level was reduced significantly by 17% (HFHC; 346830.9+/-52915.8 microm2 vs. HFHC plus losartan; 255965.3+/-74057.7 microm2, p<0.05) in the losartan-treated group. Simvastatin and simvastatin plus losartan treatments reduced macrophage infiltration into lesions by 33% (HFHC; 183575.6+/-43211.2 microm2 vs. HFHC plus simvastatin; 120556.0+/-39282.8 microm2, p<0.05) and 44% (HFHC; 183575.6+/-43211.2 microm2 vs. HFHC plus simvastatin and losartan; 103229.0+/-8473.3 microm2, p<0.001, respectively). In mice fed the HFHC diet alone, the smooth muscle cell layer in the aortic media was almost undetectable. In mice co-treated with losartan and simvastatin, the smooth muscle layer was more than 60% preserved (p<0.05). Given alone, losartan showed a slightly stronger effect than simvastatin; however, treatment with losartan plus simvastatin induced a greater inhibitory effect on atherosclerosis than either drug given alone. Serum lipid profiles did not differ significantly among the groups. CONCLUSION: Losartan displayed anti-atherosclerotic effects in apoE-/- mice that were equivalent to or greater than the effects of simvastatin. Combined treatment with these drugs had greater effect than either drug alone.

The Prevalence and Severity of Neuropsychiatric Symptoms in Alzheimer's Disease and Subcortical Vascular Dementia : the CREDOS Study

OBJECTIVES: This study aimed to compare the prevalence and severity of clinically relevant neuropsychiatric symptoms between subjects with Alzheimer's disease (AD) and subcortical vascular dementia (SVD). METHODS: The CREDOS (Clinical Research for Dementia Of South Korea) is a multicenter longitudinal cohort study organized to evaluate the long-term outcome of dementia patients. Out of a total 3,080 subjects, we selected 1,392 AD subjects and 247 SVD subjects with mild to moderate levels of dementia. The Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating Scale (CDR), and CDR sum of box scores were used for evaluation. RESULTS: After controlling for severity of dementia and duration of education, SVD subjects had relatively more symptoms of apathy compared to AD subjects (OR : 1.397, p=0.025). SVD subjects also had relatively higher NPI composite scores in the apathy domain compared to AD subjects, after controlling for severity of dementia, age and duration of education (F=7.88, p=0.01). Subjects with moderate levels of dementia had more frequent and severe neuropsychiatric symptoms compared to those with mild dementia. CONCLUSION: Symptoms of apathy were more prevalent and severe in subjects with SVD, compared to subjects with AD.

A Case of Steroid Myopathy

Steroid mvopathy is a skeletal muscle disease that develops in condition both endogenous and exogenous glucocorticoid excess and is characterized by muscle weakness. Myalgia, and wasting. The onset is usually insidious and the distribution of weakness is primarily proximal uith the legs more severely involved than the arms; cranial-nerve-in nervated muscles and sphin ers are usually spared. We report a 60-year-old man with rheumatoid arthritis uho was managed by prednisone and dexamethasone over 20 years and showed progressive lower limb weakness afterwards.