A novel 4'-brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR/ERK1/2/STAT3 pathways in non-small-cell lung cancer without any adverse effects in mice.

The therapeutic toxicity and resistance to currently available treatment options are major clinical challenges for the management of lung cancer. As a novel strategy, we synthesized analogues of a known flavonol, fisetin, which has shown anti-tumorigenic potential against cancer in cell culture with no adverse effects in animal models. We studied the synthetic analogues of fisetin for their anti-cancer potential against lung cancer cells, toxicity in mice and efficacy in a xenograft model. Brominated fisetin analogues were screened for their effects on the viability of A549 and H1299 lung cancer cells, and three analogues (3a, 3b, 3c), showed improved activity compared to fisetin. These analogues were more effective in restricting lung cancer cell proliferation, inducing G2 M phase cell cycle arrest and apoptosis. The fisetin analogues also downregulated EGFR/ERK1/2/STAT3 pathways. Fisetin analogue-induced apoptosis was accompanied by a higher Bax to Bcl-2 expression ratio. Based on the in vitro studies, the most effective fisetin analogue 3b was evaluated for in vivo toxicity, wherein it did not show any hepatotoxicity or adverse health effects in mice. Furthermore, analogue 3b showed greater antitumor efficacy (p < .001) as compared to its parent compound fisetin in a human lung cancer cell xenograft study in athymic mice. Together, our data suggest that the novel fisetin analogue 3b is more effective in restricting lung cancer cell growth, both in vitro as well as in vivo, without any apparent toxicity, supporting its further development as a novel anti-lung cancer agent.

A multimedia mobile phone-based youth smoking cessation intervention: findings from content development and piloting studies.

BACKGROUND: While most young people who smoke want to quit, few access cessation support services. Mobile phone-based cessation programs are ideal for young people: mobile phones are the most common means of peer communication, and messages can be delivered in an anonymous manner, anywhere, anytime. Following the success of our text messaging smoking cessation program, we developed an innovative multimedia mobile phone smoking cessation intervention. OBJECTIVE: The aim of the study was to develop and pilot test a youth-oriented multimedia smoking cessation intervention delivered solely by mobile phone. METHODS: Development included creating content and building the technology platform. Content development was overseen by an expert group who advised on youth development principles, observational learning (from social cognitive theory), effective smoking cessation interventions, and social marketing. Young people participated in three content development phases (consultation via focus groups and an online survey, content pre-testing, and selection of role models). Video and text messages were then developed, incorporating the findings from this research. Information technology systems were established to support the delivery of the multimedia messages by mobile phone. A pilot study using an abbreviated 4-week program of video and text content tested the reliability of the systems and the acceptability of the intervention. RESULTS: Approximately 180 young people participated in the consultation phase. There was a high priority placed on music for relaxation (75%) and an interest in interacting with others in the program (40% would read messages, 36% would read a blog). Findings from the pre-testing phase (n = 41) included the importance of selecting "real" and "honest" role models with believable stories, and an interest in animations (37%). Of the 15 participants who took part in the pilot study, 13 (87%) were available for follow-up interviews at 4 weeks: 12 participants liked the program or liked it most of the time and found the role model to be believable; 7 liked the role model video messages (5 were unsure); 8 used the extra assistance for cravings; and 9 were happy with two messages per day. Nine participants (60%) stopped smoking during the program. Some technical challenges were encountered during the pilot study. CONCLUSIONS: A multimedia mobile phone smoking cessation program is technically feasible, and the content developed is appropriate for this medium and is acceptable to our target population. These results have informed the design of a 6-month intervention currently being evaluated for its effectiveness in increasing smoking cessation rates in young people.