The common diabetes drug metformin can diminish the action of citral against Rhabdomyosarcoma cells in vitro.

Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma most commonly found in pediatric patients. Despite progress, new and improved drug regimens are needed to increase survival rates. Citral, a natural product plant oil can induce cell death in cancer cells. Another compound, metformin, isolated originally from French lilac and used by diabetics, has been shown to reduce the incidence of cancer in these patients. Application of citral to RMS cells showed increase in cell death, and RD and RH30 cells showed half maximal inhibitory concentration (IC50 ) values as low as 36.28 µM and 62.37 µM, respectively. It was also shown that the citral initiated cell apoptosis through an increase in reactive oxygen species (ROS) and free calcium. In comparison, metformin only showed moderate cell death in RMS cell lines at a very high concentration (1,000 µM). Combinatorial experiments, however, indicated that citral and metformin worked antagonistically when used together. In particular, the ability of metformin to quench the ROS induced by citral could lead to the suppression of activity. These results clearly indicate that while clinical use of citral is a promising anti-tumor therapy, caution should be exercised in patients using metformin for diabetes.

Smoking habits and coenzyme Q10 status in healthy European adults.

INTRODUCTION: Coenzyme Q10 (CoQ10) is a lipophilic endogenously synthesised antioxidant that is present in nearly all human tissues and plays an important role in mitochondrial energy production. It has been postulated that smoking has a consumptive effect on CoQ10. MATERIAL AND METHODS: To further define the relation between smoking and the serum CoQ10 status, 276 healthy volunteers aged 19 to 62 years were grouped into non-smokers (n = 113; 77 male, 36 female) and smokers (n = 163; 102 male, 61 female). Serum lipid profile was analysed by standard clinical chemistry. Coenzyme Q10 concentration and redox status were analysed by high-pressure liquid chromatography with electrochemical detection. RESULTS: Male smokers showed higher serum CoQ10 levels than female smokers. This sex-related difference was accounted for when CoQ10 was related to low-density lipoprotein (LDL) cholesterol as the main carrier of CoQ10 in the circulation. Neither LDL-adjusted CoQ10 concentration nor redox status significantly differed when smokers and non-smokers were compared. Regarding the smoking history, the number of cigarettes consumed per day did not significantly affect the CoQ10 status. Interestingly, with increasing time of smoking habit we observed increasing levels of LDL-adjusted serum CoQ10 concentration (Spearman's p < 0.002) and of the reduced form of CoQ10 (Spearman's p < 0.0001). CONCLUSIONS: As an adaptive response to oxidative stress in long-term smokers an increased demand for antioxidant capacity may be covered by increasing levels of LDL-adjusted CoQ10 serum concentrations and by a concomitantly increased availability of the reduced, active form of CoQ10, possibly by induction of enzymes that are involved in converting CoQ10ox to CoQ10red.

Coenzyme Q10 redox state predicts the concentration of c-reactive protein in a large caucasian cohort.

In the present study the relationship between the CoQ10 redox state (% oxidized form of CoQ10 ) and the serum level of c-reactive protein (CRP) was investigated in a large Caucasian study population (n = 1319). In order to evaluate independently the influence of the variables that predict the outcome of CRP, an analysis of covariance (ANCOVA) was performed with CRP as the dependent variable. Gender was taken as an independent factor and CoQ10 redox and BMI as independent covariates. Results were substantiated with findings from a human intervention study (n = 53), receiving 150 mg/day ubiquinol for 14 days. Spearman's correlation revealed a significant (P < 0.001) association between the CoQ10 redox state and CRP concentrations in the whole study population. Thus, higher CRP concentrations were found in subjects having more oxidized CoQ10 . Similar results were evident for further inflammatory markers (interleukin-6, number of leucocytes). The ANCOVA revealed a significant (P < 0.001) prediction of CRP concentrations by CoQ10 redox state, after controlling for the effect of BMI and separately for gender. In the intervention study it was further found that the oral intake of ubiquinol increased its proportion significantly (P < 0.001), with the highest increase in those persons having a low basal serum ubiquinol content (<92.3%). Here it was discovered that the ubiquinol status significantly correlated to the concentration of the inflammation marker monocyte chemotactic protein 1. It is concluded that CoQ10 redox state predicts the concentration of CRP. Persons at risk with lower ubiquinol status, higher BMI, and low grade inflammation may benefit from ubiquinol supplementation. © 2016 BioFactors, 42(3):268-276, 2016.

Determination of the coenzyme Q10 status in a large Caucasian study population.

Coenzyme Q10 (CoQ10 ) exists in a reduced (ubiquinol) and an oxidized (ubiquinone) form in all human tissues and functions, amongst others, in the respiratory chain, redox-cycles, and gene expression. As the status of CoQ10 is an important risk factor for several diseases, here we determined the CoQ10 status (ubiquinol, ubiquinone) in a large Caucasian study population (n = 1,911). The study population covers a wide age range (age: 18-83 years, 43.4% men), has information available on more than 10 measured clinical phenotypes, more than 30 diseases (presence vs. absence), about 30 biomarkers, and comprehensive genetic information including whole-genome SNP typing (>891,000 SNPs). The major aim of this long-term resource in CoQ10 research is the comprehensive analysis of the CoQ10 status with respect to integrated health parameters (i.e., fat metabolism, inflammation), disease-related biomarkers (i.e., liver enzymes, marker for heart failure), common diseases (i.e., neuropathy, myocardial infarction), and genetic risk in humans. Based on disease status, biomarkers, and genetic variants, our cohort is also useful to perform Mendelian randomisation approaches. In conclusion, the present study population is a promising resource to gain deeper insight into CoQ10 status in human health and disease.