Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells.

The anti-proliferative effects of 5-methylquinolinium (5MQ) of nicotinamide N-methyltransferase (NNMT) have not been previously investigated on a cervical cancer cell line. NNMT is a metabolic enzyme that is correlated with tumour progression and metastasis. 5MQ is a small molecule inhibitor of NNMT. 0.1-500 µM of 5MQ was tested on the HeLa epithelial cervical cancer cell line. Cell viability was assessed with the MTT test. TWIST, ZEB1, SERPIN1, SIRT1, CD16, mRNA and various protein expression levels were analysed with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively. 5MQ significantly inhibited HeLa cell proliferation in a concentration and time-dependent manner. Increased cell shrinkage, loss of cellular adhesions and apoptotic bodies were observed in HeLa cells after 5MQ treatment. Following treatment with 5MQ, ZEB1, SIRT1, CD16 mRNA levels were increased while TWIST and SERPIN1 mRNA levels were reduced. Expressions of oncogenic proteins phospho-Akt and SIRT1 were decreased. 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation.IMPACT STATEMENTWhat is already known on this subject? NNMT is a cytosolic enzyme involved in tumour progression, metastasis and treatment resistance. It was overexpressed in many human malignancies. 5-amino-1-methylquinolinium (5MQ) is a novel small molecule inhibitor of NNMT that has shown promising results in the treatment of obesity and in senescent muscle regeneration. 5MQ has not been tested on the HeLa cervical cancer cell line, previously.What do the results of this study add? In this study, 5MQ was tested on the HeLa cervical cancer cell line for the first time and the molecular changes associated with 5MQ treatment were analysed. 5MQ demonstrated significant anti-proliferative activity on HeLa cells, which displayed morphological signs of apoptosis. Treatment of HeLa cells with 5MQ led to an increase in ZEB1, SIRT1 mRNA while TWIST mRNA was decreased. Phospho-Akt and Sirtuin1 protein expressions were decreased.What are the implications of these findings for clinical practice and/or further research? 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. 5MQ treatment was associated with a decrease in the expression of phospho-Akt and Sirtuin1 proteins, both of which have been reported to maintain tumour progression. 5MQ can further be investigated and modified for anti-cancer therapy.

Panton-Valentine leukocidin in community and hospital-acquired Staphylococcus aureus strains.

Staphylococcus aureus causes serious hospital-acquired (HA) and community-acquired (CA) infections. Skin and soft-tissue infections especially are sometimes caused by strains harbouring Panton-Valentine leukocidin (PVL). PVL belongs to a family of bi-component leukocidal toxins produced by staphylococci. It is a pore-forming toxin encoded by lukF-PV and lukS-PV. A total of 70 S. aureus strains: 38 (54%) methicillin-resistant (MRSA) and 32 (46%) methicillin-susceptible (MSSA), were isolated from patients admitted to Dicle University Hospital (Turkey). Identification of S. aureus and antibiotics-susceptibility testing were performed with PHOENIX 100. PVL genes and mecA genes were detected by polymerase chain reaction. Of the 70 studied strains, 36 ones (51%) were community acquired and 34 ones (49%) were hospital acquired . A total of 38 (54%) strains were positive for mecA (mecA+), of which 32 ones (84%) were HA. Of the mecA- strains, 30 (94%) were CA. Of the 70 studied strains, 12 (17%) strains were PVL+: 8 (22%) of the 36 CA strains and 4 (12%) of the 34 HA strains. Of the 12 PVL+ strains, 4 strains were mecA+. The PVL positivity rate was 25% in MSSA, whereas 10.5% in MRSA. Of the overall PVL+ strains, seven strains were obtained from wounds; four ones from skin abscess; and one from blood culture. Taken together, the obtained results showed a substantial level of PVL genes in the studied region. Although PVL is known as a common virulence factor of CA MRSA, HA MRSA isolates in our study showed a considerable rate of PVL positivity.