In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines

Hinokitiol is a natural component isolated from Chamacyparis taiwanensis. It has anti-microbial activity, and has been used in oral care products. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of hinokitiol against MRSA, Aggregatibacter actinomycetemcomitans, Streptococcus mutans, and Candida albicans were determined by the agar and broth dilution method (MIC: 40–110 μM; MMC: 50–130 μM); the paradoxical inhibition phenomenon (PIP) was observed in A. actinomycetemcomitans and S. mutans. The PIP can be described as microbial growth occurring in the presence of both high and low concentrations of a compound, between which microbial growth is inhibited. The PIP was confirmed using a kinetic microplate and inhibition zone methods. The PIP was also observed in MRSA. The low autolysin activity somehow correlated to the PIP positive. The cell diameter was increased in all the pathogens, and the transition was inhibited in C. albicans following hinokitiol treatment. Hinokitiol is also a potential anticancer drug. The 200 μM of hinokitiol has significant antimicrobial and cytotoxic activities against oral pathogens and oral squamous cell carcinoma cell lines, respectively, and lower cytotoxic effects for normal human oral keratinocytes, indicating that hinokitiol displays a high potential for safe and effective applications in oral health care.     

A Novel Compound NSC745885 Exerts an Anti-Tumor Effect on Tongue Cancer SAS Cells In Vitro and In Vivo

Objective

Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.

Methods

We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.

Results

Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.

Conclusions

The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.     

Optimization of ultrasound-accelerated synthesis of enzymatic octyl hydroxyphenylpropionate by response surface methodology

The ultrasound-accelerated enzymatic synthesis of octyl hydroxyphenylpropionate (OHPP) from p-hydroxyphenylpropionic acid (HPPA) and octanol was investigated in this study. A commercially available immobilized lipase from Candida antarctica, Novozym 435, was used as the biocatalyst. A three-level-three-factor Box-Behnken design experiment and response surface methodology were used to evaluate the effects of temperature, reaction time, and enzyme activity on percent yield of OHPP. The results indicated that temperature and enzyme activity significantly affected percent yield, whereas reaction time did not. A model for the synthesis of OHPP was established. Based on a ridge max analysis, the optimum conditions for OHPP synthesis were predicted to use a reaction temperature of 58.8°C, a reaction time of 14.6 h, and an enzyme activity of 410.5 PLU with a yield of 98.5%. A reaction was performed under these optimal conditions, and a yield of 97.5% ± 0.1% was obtained.     

Herpesvirus-induced cell fusion that is dependent on cell surface heparan sulfate or soluble heparin.

The entry of enveloped viruses into animal cells and the cell-to-cell spread of infection via cell fusion require the membrane-fusing activity of viral glycoproteins. This activity can be dependent on variable cell factors or triggered by environmental factors. Here we show that cell fusion induced by herpes simplex virus glycoproteins is dependent on the presence of cell surface glycosaminoglycans, principally heparan sulfate, or on the addition of heparin to the medium. The role of the glycosaminoglycan is probably to alter the conformation of a viral heparin-binding glycoprotein required for the fusion.     

Increased oxidazability of plasma low density lipoprotein from patients with coronary artery disease

Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu²⁺ oxidation of lipoproteins monitored by changes in fluorescenece, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While VLDL and LDL of normal controls were oxidazed at 5–10 μM Cu²⁺, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1–2.5 μM Cu²⁺, i.e., at relatively lowver oxidative stress. At 5 μM Cu²⁺, VLDL and LDL of patients with coronary artery disease still showed at faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasm VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of health persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be important factor influencing the development of coronary artery disease.