Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin's biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35–250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3-dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co-regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/ agent for cancer chemotherapy.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Death* ; Cell Survival ; Drug Therapy ; Far East ; Humans* ; Lithospermum ; Phosphotransferases ; Reactive Oxygen Species ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Stomach Neoplasms ; Stomach* ; Transfection

OBJECTIVES: There are only a limited number of studies on instruments assessing fatigue in university students, although fatigue exerts negative influences on their health and academic performances and fatigue-related complaints are more frequently reported in young adults than middle-aged adults. The aim of this study was to validate the 9-item Fatigue Severity Scale (FSS) among university students including both undergraduate and graduate students in South Korea. METHODS: A total of 176 university students completed a battery of self-report questionnaires, including the FSS, the Brief Fatigue Inventory (BFI), the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), the Medical Outcomes Study Short Form 36 version 2 (MOS-SF36v2), and the Inclusion of Community in the Self Scale (ICS). The data were collected from February of 2012 to June of 2012. The reliability, convergent validity, divergent validity, and exploratory factor analyses were conducted to assess psychometric properties of the FSS. RESULTS: The mean FSS score was 3.20 (standard deviation = 1.43). The FSS demonstrated an excellent internal consistency (Cronbach's alpha = 0.93) and item-total correlations ranged from 0.56 to 0.90. Correlations of the FSS with the BFI (r = 0.71, p < 0.01), BDI-II (r = 0.54, p < 0.01), BAI (r = 0.46, p < 0.01), MOS-SF36v2 physical component summary (r = -0.28, p < 0.01), MOS-SF36v2 mental component summary (r = -0.55, p < 0.01), and ICS (Spearman's rho = -0.07, p = 0.33) showed acceptable convergent and divergent validity. Exploratory factor analysis defined one underlying factor (eigenvalue = 5.67) that explained 93.50% of the total variance. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate reliability and validity of the FSS in university students. The FSS exhibits good psychometric properties for evaluation of fatigue among university students in South Korea. Since the FSS is easy to administer, score, and interpret, it could be a useful tool in research and practice for assessing fatigue among university students.
Adult ; Anxiety ; Depression ; Fatigue ; Humans ; Psychometrics ; Reproducibility of Results ; Republic of Korea ; Young Adult ; Surveys and Questionnaires