Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical Genes Involved in Apoptotic Pathways.

Purpose: Sepantronium bromide (YM155) is a Survivin inhibitor which recently advanced as an anticancer agent in phase II clinical trials. Survivin belongs to IAP (inhibitor of apoptosis) gene family and is a pivotal target for treatment due to its overexpression and oncogenic function in many malignancies, including acute lymphoblastic leukemia (ALL). Although survivin is a specific target for YM155, recent reports have shown that it has many other crucial targets that regulate its anti-apoptotic effects. The aim of this study was to investigate whether YM155 could have an effect on cell death-inducing genes as well as inducing apoptosis in T-ALL MOLT4- cell line. Methods: We treated MOLT-4 cells with increasing concentrations of YM155 and then cell viability was determined using MTT (methyl thiazolyl tetrazolium) assay. Also, the rate of induction of apoptosis in MOLT-4 cells and the target genes expression levels were evaluated by Annexin V/PI and real-time PCR, respectively. Results: YM155 inhibited cell growth in MOLT-4 cells. This outcome is achieved by inducing apoptosis and a significant increase in the expression level of P53, MiR-9, caspase 3 and decreasing the mRNA expression levels of survivin, Sirtuin1(SIRT1), member of anti-apoptotic proteins family (Bcl-2), and epithelial-to-mesenchymal transition (EMT) initiating factors Snail1and Zeb2. Conclusion: The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction.

Emerging molecular functions of microRNA-124: Cancer pathology and therapeutic implications.

MicroRNAs are characterized as small, single-stranded, non-coding RNA molecules that bind to their target mRNA to prevent protein synthesis. MicroRNAs regulate various normal processes; however, they are aberrantly regulated in many cancers. They control the expression of various genes, including cancer-related genes. This causes microRNAs to be considered as a good target for further investigations for designing novel therapeutic strategies. Since miR124 is known for some time already, it has a tumor-suppressing role in various cancers. Numerous studies indicate its definite roles in malignant processes such as epithelial-to-mesenchymal transition, cell cycle arrest, metastasis, cancer stem cell formation and induction of apoptosis. However, some studies have indicated a dual role for miR-124 in oncogenic processes like autophagy and multi-drug resistance. In this article, we will review recent researches on the biological functions and clinical implications of miR-124. Subsequently, we will discuss future perspectives in terms of the roles of this miRNA in cancers.

Relationship between bone density and abdominal visceral fat in premenopausal overweight and obese Iranian women aged 30-50 years.

AIM: The presence of a direct relationship between body mass index (BMI) and bone mineral density (BMD) is frequently reported. However, data on the relationship between visceral fat and bone density varies, with positive, negative or no relationship having been reported. This study aims to examine the relationship between abdominal visceral fat and BMD. METHODS: A cross sectional study was carried out on 95 premenopausal, overweight and obese women aged 30-50 years referred to Sina Hospital, Tehran, Iran in 2011-2012. Anthropometric indices and visceral fat levels were measured. RESULTS: Multiple linear regression analysis showed that proximal femur BMD (P = 0.856) and lumbar spine BMD (P = 0.558) were not significantly related to visceral fat level. However, BMI had a direct and significant positive relationship with proximal femur BMD (P = 0.001) and lumbar spine BMD (P = 0.031). Menarche age was negatively related to lumbar spine BMD (P = 0.003). CONCLUSIONS: In this study, after adjusting for fat-free mass, no significant relationship was found between MBD of the proximal femur and lumbar spine, and visceral fat level or visceral fat to total fat percentage ratio. Therefore, abdominal visceral fat may not affect BMD, independent of weight. It seems that the positive relationship between BMI and proximal femur and lumbar spine BMD is due to the mechanical effects of weight on bones.