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Publication
Journal: Gynecologic Oncology
November/1/2006
Abstract
OBJECTIVE
Epithelial ovarian cancer has the highest mortality rate among gynecologic cancers. Chemotherapy is an essential component of its treatment. While isothiocyanates are known to possess chemopreventive effects against various cancers, yet little is known about their chemotherapeutic potential in ovarian cancer (OC). In the present study, we examined the antiproliferative and apoptotic effect of phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate on OVCAR-3 cells.
METHODS
Cytotoxic activity of PEITC on OVCAR-3 cells was determined using cell proliferation, apoptosis (DNA fragmentation and TUNEL assay) and caspase-activation studies. The role of PARP-1, Bax, and Bcl-2 in apoptosis was analyzed by Western blotting. Activation of JNK1/2, p38, Akt, ERK1/2, and c-Myc was examined by immunoblotting. Specific inhibitors of caspases, JNK1/2, p38, and MEK were used to corroborate these data.
RESULTS
PEITC was cytotoxic to OVCAR-3 cells, and inhibited proliferation in a dose-dependent fashion (IC(50) = 23.2 microM). PEITC induced apoptosis by activating caspase-3 and -9, without capsase-8 activation. Anti-apoptotic Bcl-2 levels were suppressed while pro-apoptotic Bax levels were enhanced. PEITC suppressed activation of Akt, ERK1/2, and the expression of transcription factor c-Myc, while simultaneously activating pro-apoptotic p38 and JNK1/2. Specific inhibitors of caspase-3 and -9, JNK1/2, and p38 reversed the cytotoxic effect of PEITC.
CONCLUSIONS
These findings demonstrate that PEITC exhibits cytotoxicity towards OVCAR-3 cells and induces apoptosis via caspase-9 and -3 pathways. PEITC inhibits Akt, ERK1/2 survival signaling, and c-Myc while simultaneously activating pro-apoptotic p38 and JNK1/2. Systematic preclinical and clinical trials with PEITC in ovarian cancer are indicated.
Publication
Journal: Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors
September/26/2010
Abstract
Previous randomized controlled trials have not supported moderate intensity exercise as an efficacious adjunct to smoking cessation treatments for women; however, compliance with exercise programs in these studies has been poor. The purpose of this pilot study was to estimate the effects of moderate intensity exercise on smoking cessation outcomes under optimal conditions for exercise program compliance. Sixty previously sedentary, healthy, female smokers were randomized to an 8-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either 150 min/week of moderate intensity exercise or contact control. Participants attended a median of 86.4% and 95.5% of prescribed exercise/control sessions, respectively. There was a moderate, though statistically nonsignificant, effect of exercise at post-treatment for objectively verified 7-day point prevalence abstinence (48.3% vs. 23.3%; OR = 3.07, 95% CI: 0.89-11.07) and prolonged abstinence (34.5% vs. 20.0%; OR = 2.11, 95% CI: 0.56-8.32). Effects were attenuated when controlling for potential confounders, and after a 1-month, no-treatment period. The findings provide a preliminary indication that, given adequate compliance, moderate intensity exercise may enhance short-term smoking cessation outcomes for women; however, a larger trial is warranted.
Publication
Journal: Addictive Behaviors
September/18/2011
Abstract
A growing number of laboratory studies have shown that acute bouts of aerobic exercise favorably impact affect and cravings among smokers. However, randomized trials have generally shown exercise to have no favorable effect on smoking cessation or withdrawal symptoms during quit attempts. The purpose of the present study was to explore this apparent contradiction by assessing acute changes in affect and cravings immediately prior to and following each exercise and contact control session during an eight-week smoking cessation trial. Sixty previously low-active, healthy, female smokers were randomized to an eight-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either three sessions/week of moderate intensity aerobic exercise or contact control. Findings revealed a favorable impact of exercise on acute changes in positive activated affect (i.e., energy), negative deactivated affect (i.e., tiredness), and cigarette cravings relative to contact control. However, effects dissipated from session to session. Results suggest that aerobic exercise has potential as a smoking cessation treatment, but that it must be engaged in frequently and consistently over time in order to derive benefits. Thus, it is not surprising that previous randomized controlled trials-in which adherence to exercise programs has generally been poor-have been unsuccessful in showing effects of aerobic exercise on smoking cessation outcomes.