Induction of epigenetic alteration by CPUK02, an Ent- kaurenoid derivative of stevioside

Background: Dietary polyphenols, such as those found in green tea and red wine, are linked to antitumor activity. They are known to influence many signaling pathways epigenetically within the human body. In this regard, CPUK02 [15-Oxosteviol benzyl ester] is a new ent-kaurenoid derivative of stevioside and exhibits strong anti-cancer activity in vitro and in vivo. Nowadays, the role of epigenetics in cancer has been the subject of intensive study and DNA methylation targeting represents a relevant strategy for cancer treatment. There are no reports regarding the effects of CPUK02 on epigenetic alterations in colorectal cancer cell line. This study was an attempt to compare CPUK02 with 5-AZA as DNMT inhibitor agent and evaluate whether it can induce its anti-cancer effects via altering the level of DNMT3b mRNA, MGMT and SFRP2 methylation pattern in HCT 116 cell line

Methods: To evaluate DNMT3b expression, DNMT3B mRNA levels in HCT116 CRC cell line were quantified by real-time reverse-transcriptase Polymerase Chain Reaction [PCR] assay after 24 hr of incubation time with CPUK02 and 5-AZA. In addition, the methylation patterns of 2 CpG islands in this cell line were examined by methylation specific PCR methods

Results: CPUK02 surprisingly, decreased the DNMT3b mRNA level. The average expression levels of DNMT3b in HCT116 treated with CPUK02 and 5-AZA relative to the GAPDH expression level in control were 0.16 and 0.5%, respectively. Furthermore, CPUK02 could decrease the methylated allele of MGMT and SFRP2 genes in HCT 116 after 24 hr

Conclusion: In this study, positive correlation was found between mRNA expression of DNMT3b and gene promoter hypermethylation after treatment with CPUK02 and 5-AZA. Our data confirmed that CPUK02 like 5-AZA exhibits demethylating properties

Retrospective Comparison of Levofloxacin and Moxifloxacin on Multidrug-Resistant Tuberculosis Treatment Outcomes

BACKGROUND/AIMS: To compare the effect of levofloxacin and moxifloxacin on treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: A retrospective analysis of 171 patients with MDR-TB receiving either levofloxacin or moxifloxacin was performed. Treatment responses were categorized into treatment success (cured and treatment completed) or adverse treatment outcome (death, failure, and relapsed). RESULTS: The median age of the patients was 42.0 years. Approximately 56% of the patients were male. Seventeen patients had extensively drug-resistant tuberculosis, and 20 had a surgical resection. A total of 123 patients (71.9%) received levofloxacin for a median 594 days, and 48 patients (28.1%) received moxifloxacin for a median 673 days. Other baseline demographic, clinical, and radiographic characteristics were similar between the two groups. The moxifloxacin group had a significantly higher number of resistant drugs (p < 0.001) and a higher incidence of resistance to ofloxacin (p = 0.005) in the drug sensitivity test. The treatment success rate was 78.9% in the levofloxacin group and 83.3% in the moxifloxacin group (p = 0.42). Adverse reactions occurred at similar rates in the groups (p = 0.44). Patients in the moxifloxacin group were not more likely to have treatment success than those in the levofloxacin group (adjusted odds ratio, 0.76; 95% confidence interval, 0.24 to 2.43; p = 0.65). CONCLUSIONS: Both levofloxacin and moxifloxacin showed equivalent efficacy for treating MDR-TB.