Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy

<p>Abstract</p> <p>Background</p> <p>Lipoic acid (LA), a potent antioxidant, has been used as a dietary supplement to prevent and treat many diseases, including stroke, diabetes, neurodegenerative and hepatic disorders. Recently, potent anti-tumorigenic effects induced by LA were also reported and evident as assayed by suppression of cell proliferation and induction of apoptosis in malignant cells. However, the mechanism by which LA elicits its chemopreventive effects remains unclear.</p> <p>Methods and Results</p> <p>Herein, we investigated whether LA elicits its anti-tumor effects by inducing cell cycle arrest and cell death in human promyelocytic HL-60 cells. The results showed that LA inhibits both cell growth and viability in a time- and dose-dependent manner. Disruption of the G₁/S and G₂/M phases of cell cycle progression accompanied by the induction of apoptosis was also observed following LA treatment. Cell cycle arrest by LA was correlated with dose-dependent down regulation of Rb phosphorylation, likely via suppression of E2F-dependent cell cycle progression with an accompanying inhibition of cyclin E/cdk2 and cyclin B1/cdk1 levels. Evidence supporting the induction of apoptosis by LA was based on the appearance of sub-G₁peak in flow cytometry analysis and the cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product in immunoblot assays. Apoptosis elicited by LA was preceded by diminution in the expression of anti-apoptotic protein bcl-2 and increased expression of apoptogenic protein bax, and also the release and translocation of apoptosis inducing factor AIF and cytochrome c from the mitochondria to the nucleus, without altering the subcellular distribution of the caspases.</p> <p>Conclusion</p> <p>This study provides evidence that LA induces multiple cell cycle checkpoint arrest and caspase-independent cell death in HL-60 cells, in support of its efficacious potential as a chemopreventive agent.</p

The effect of alcohol advertising, marketing and portrayal on drinking behaviour in young people: systematic review of prospective cohort studies

<p>Abstract</p> <p>Background</p> <p>The effect of alcohol portrayals and advertising on the drinking behaviour of young people is a matter of much debate. We evaluated the relationship between exposure to alcohol advertising, marketing and portrayal on subsequent drinking behaviour in young people by systematic review of cohort (longitudinal) studies.</p> <p>Methods</p> <p>studies were identified in October 2006 by searches of electronic databases, with no date restriction, supplemented with hand searches of reference lists of retrieved articles. Cohort studies that evaluated exposure to advertising or marketing or alcohol portrayals and drinking at baseline and assessed drinking behaviour at follow-up in young people were selected and reviewed.</p> <p>Results</p> <p>seven cohort studies that followed up more than 13,000 young people aged 10 to 26 years old were reviewed. The studies evaluated a range of different alcohol advertisement and marketing exposures including print and broadcast media. Two studies measured the hours of TV and music video viewing. All measured drinking behaviour using a variety of outcome measures. Two studies evaluated drinkers and non-drinkers separately. Baseline non-drinkers were significantly more likely to have become a drinker at follow-up with greater exposure to alcohol advertisements. There was little difference in drinking frequency at follow-up in baseline drinkers. In studies that included drinkers and non-drinkers, increased exposure at baseline led to significant increased risk of drinking at follow-up. The strength of the relationship varied between studies but effect sizes were generally modest. All studies controlled for age and gender, however potential confounding factors adjusted for in analyses varied from study to study. Important risk factors such as peer drinking and parental attitudes and behaviour were not adequately accounted for in some studies.</p> <p>Conclusion</p> <p>data from prospective cohort studies suggest there is an association between exposure to alcohol advertising or promotional activity and subsequent alcohol consumption in young people. Inferences about the modest effect sizes found are limited by the potential influence of residual or unmeasured confounding.</p

Identifying perceived barriers to monitoring service quality among substance abuse treatment providers in South Africa

Background: A performance measurement system is planned for South African substance abuse treatment services. Provider-level barriers to implementing these systems have been identified in the United States, but little is known about the nature of these barriers in South Africa. This study explored the willingness of South African substance abuse treatment providers' to adopt a performance measurement system and perceived barriers to monitoring service quality that would need to be addressed during system development. Methods: Three focus group discussions were held with treatment providers from two of the nine provinces in South Africa. These providers represented the diverse spread of substance abuse treatment services available in the country. The final sample comprised 21 representatives from 12 treatment facilities: eight treatment centres in the Western Cape and four in KwaZulu-Natal. Content analysis was used to extract core themes from these discussions. Results: Participants identified barriers to the monitoring of service quality that included outdated modes of collecting data, personnel who were already burdened by paperwork, lack of time to collect data, and limited skills to analyse and interpret data. Participants recommended that developers engage with service providers in a participatory manner to ensure that service providers are invested in the proposed performance measurement system. Conclusion: Findings show that substance abuse treatment providers are willing to adopt a performance measurement system and highlight several barriers that need to be addressed during system development in order to enhance the likelihood that this system will be successfully implemented. © 2014 Myers et al.; licensee BioMed Central Ltd