Induction of apoptosis in tumor cells by three naphthoquinone esters isolated from Thai medicinal plant: Rhinacanthus nasutus KURZ

Rhinacanthus nasutus KURZ. (Acanthaceae) has been used as Thai traditional medicine for the treatment of various cancers. Recently, we reported that rhinacanthins, active components of the plant, had antiproliferative activity against human cancer line cells. In the present study, we investigated the growth inhibitory mechanism of rhinacanthins-C, -N and -Q, three main naphthoquinone esters isolated from the roots of R. nasutus KURZ. in human cervical carcinoma (HeLaS3) cells by means of TUNEL staining, DNA fragmentation assay, flow cytometry, and cleavage assay of Asp-Glu-Val-Asp-peptide-nitroanilide, a caspase-3 substrate. After the HeLaS3 cells was exposed with different concentrations of the drugs, rhinacanthins-C, -N and -Q exhibited antiproliferative effects on HeLaS3 cells with the IC50 values of 80, 65, 73 microM; 55, 45, 55 microM; and 1.5, 1.5 and 5.0 microM for 24, 48 and 72 h time points, respectively. Morphological changes showing nuclear fragmentation of rhinacanthins-treated cells were clearly observed after 48 h exposure. Consistent with this observation, the appearance of a ladder formation was also evident with an agarose gel electrophoresis of the extracted DNA. Flow cytometric analysis revealed that rhinacanthin-N caused G2/M arrest of HeLaS3 cells after 24 h incubation, and increased the proportion of sub-G1 hypodiploid cells, apoptotic cells, in the population of HeLaS3 cells after 48 and 72 h incubation. Moreover, the drug treatment markedly elevated the activity of caspase-3. Based on these results, our findings demonstrated for the first time that the inhibitory effects of three main naphthoquinone esters isolated from the roots of R. nasutus KURZ. on the growth of HeLaS3 cells appear to arise from the induction of apoptosis, that might be associated with the activation of caspase-3 pathway.     

Antitumor activity of liposomal naphthoquinone esters isolated from Thai medicinal plant: Rhinacanthus nasutus KURZ

We previously observed that rhinacanthins-C, -N and -Q, three main naphthoquinone esters isolated from the roots of Thai medicinal plant; Rhinacanthus nasutus KURZ. (Acanthaceae) induced apoptosis of human cervical carcinoma HeLaS3 cells. Since these rhinacanthins showed limited solubility in aqueous medium, we attempted to entrap them into liposomal membrane: Liposomalization enabled injection of the drugs and the drugs were expected to transfer to lipoproteins in the bloodstream. Liposomal formulations of rhinacanthins-C, -N and -Q showed strong antiproliferative activity against HeLaS3 cells with the IC50 values of 32, 17, 70 microM; 19, 17, 52 microM and 2.7, 2.0 and 5.0 microM for the exposure time of 24, 48, and 72 h, respectively. These liposomes suppressed the tumor growth in Meth-A sarcoma-bearing BALB/c mice at the dose of 5.0 mg/kg/d for 10 d. Among rhinacanthins, liposomal rhinacanthin-N significantly suppressed solid tumor growth. Based on these results, our findings demonstrated that rhinacanthin-N suppressed tumor growth in vivo, and suggested that liposomes are useful for preparing injectable formulation of hydrophobic drugs.     

Preoperative carcinoembryonic antigen and albumin in predicting survival in patients with colon and rectal carcinomas

OBJECTIVE: To examine the relationship between postoperative outcomes of colorectal carcinoma patients and preoperative serum carcinoembryonic antigen (CEA) and albumin (ALB) levels and evaluate if these levels can accurately predict outcomes and/or be factor indicating adjuvant chemotherapy. BACKGROUND: CEA is a marker for colorectal carcinoma and its level usually increases before a distant metastasis is detected. Also, a low level of serum ALB is usually found in metastatic colorectal carcinoma patients. STUDY: A retrospective cohort study of patients with colorectal carcinomas who were treated with curative surgery in Songklanagarind Hospital between 1998 and 2002. RESULTS: One hundred seventy patients were identified with a median survival of 1131 days (range 71 to 2293 d) and with an overall 5-year survival rate of 54%. Patients were stratified using CEA at 5 ng/mL and an ALB level at 3.5 g/dL into 4 groups: (1) low CEA, high ALB; (2) low CEA, low ALB; (3) high CEA, high ALB; and (4) high CEA, low ALB. The 5-year survival rates for groups 1 to 4 were 66%, 63%, 46%, and 34%, respectively. There was statistically significant difference in 5-year survival between the well-differentiated tumor with low CEA and the poorly differentiated tumor with high CEA (P=0.0115). The high CEA patients who had the well-differentiated tumor had longer survival than those with a poorly differentiated tumor (P=0.0412). CONCLUSIONS: A preoperative CEA level greater than or equal to 5 ng/mL and ALB level less than 3.5 g/dL predict a poor survival chance for colorectal carcinoma patients. In high CEA patients, tumor differentiated is an independent factor affecting survival.     

PPARγ activator,rosiglitazone: Is it beneficial or harmful to the cardiovascular system?

Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity.Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction,inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation,and the protection of myocardial injury during ischemic/reperfusion in different animal models.Previous clinical studies in typeⅡdiabetes patients demonstrated that rosiglitazone played an important role in protectingagainst arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system.Despite these benefits,inconsistent findings have been reported,and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system,including increased risk of acute myocardial infarction,heart failure and chronic heart failure.As a result,rosiglitazone has been recently withdrawn from EU countries.Nevertheless,the effect of rosiglitazone on ischemic heart disease has not yet been firmly established.Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.     

Four new xanthones and their cytotoxicity from the stems of Garcinia schomburgkiana

Journal of Natural Medicines - Four new xanthones, named schomburgones C-F (1‒4), along with six known xanthones (5‒10) were isolated from the stems of Garcinia schomburgkiana. Their...     

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.     

Electroacupuncture versus Diclofenac in symptomatic treatment of Osteoarthritis of the knee: a randomized controlled trial

Background  

The purpose of this study was to compare the efficacy of electroacupuncture (EA), diclofenac and their combination in symptomatic treatment of osteoarthritis (OA) of the knee.