Enhancement of antitumor effects of a new boron compound combined with ultrasound on the mouse ascites tumor.

The use of ultrasound in therapeutic medicine is a developing field. The action of many anticancer agents can be improved with the use of ultrasonic exposure either in vitro or in vivo. Boron-based compounds have shown promising results as chemotherapeutic agents in specific forms of cancer. We synthesized a new boron compound of chloroacetohydroxamic acid, 2-hydroxyamino-oxoethylborate (HAOB). HAOB was used in combination with ultrasound (US) at a frequency of 25 KHz, and inhibitory effects on the growth of mouse ascites tumours were monitored by observing survival time, tumour growth, cell viability and DNA synthesis of treated Ehrlich ascites carcinoma (EAC) cells. 5-Fluorouracil (5-FU) was used as a positive control. The results indicated that HAOB alone produced significant antitumor action whereas combination of US with HAOB or 5-FU produced an extra antitumor action when compared to the actions of HAOB or 5-FU used alone.

Dexamethasone decreases temozolomide-induced apoptosis in human gliobastoma T98G cells.

Human glioblastoma is a deadly brain tumor that is often treated with a combination of drugs. A new alkylating agent, temozolomide (TMZ), has recently been found efficacious in the clinical trials for glioblastoma. Steroids, such as dexamethasone (DXM), are often used concomitantly as a supportive therapy to treat cerebral edema. However, any possible modulatory effect of the steroids on the efficacy of TMZ has not yet been evaluated experimentally. In this study, we have examined whether DXM provides synergistic or antagonistic effect on TMZ-induced apoptosis in human glioblastoma T98G cells. T98G cells were pretreated with various doses of DXM followed by TMZ. The cell viability was assessed by the trypan blue dye exclusion test. Wright staining and the TdT-mediated dUTP nick-end labeling (TUNEL) assay were used to evaluate apoptotic cell death based on the morphological and biochemical (DNA fragmentation) features, respectively. More biochemical features of apoptotic death, such as upregulation of Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity, were assessed by Western blot analysis. A significant number of T98G cells committed apoptosis after treatment with 200 microM TMZ. However, a pretreatment with 100 microM or 200 microM DXM protected T98G cells against TMZ-induced apoptosis, concomitantly decreasing Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity. These experimental results indicate that DXM works as an antagonistic agent in combination with TMZ. Therefore, our investigation strongly implies that the combination of DXM and TMZ may be counteractive in treating human glioblastoma.

Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells.

We examined the mechanism of 17beta-estradiol (estrogen)-mediated inhibition of apoptosis in C6 (rat glioma) cells following exposure to hydrogen peroxide (H(2)O(2)). Cells were preincubated with 4 microM estrogen for 2 h and then exposed to 100 microM H(2)O(2) for 24 h. Exposure to H(2)O(2) caused significant increases in intracellular calcium (Ca(2+)), as determined by fura-2, which was attenuated by preincubation with estrogen. H(2)O(2) and ionomycin caused cell death in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Preincubation with estrogen restored viability in cells exposed to H(2)O(2) but not in cells exposed to ionomycin. Western blot analysis showed an increase in Bax/Bcl-2 ratio, calpain activity, and caspase-3 activity following treatment with H(2)O(2), and estrogen pretreatment decreased levels of all three. Cell morphology, as evaluated by Wright staining, indicated apoptosis in cells treated with H(2)O(2), and pretreatment with estrogen reduced apoptosis. Results from MTT and Wright staining were further supported by the terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) assay. These results indicate a role for estrogen in preventing apoptosis in C6 glial cells exposed to H(2)O(2). Our results suggest that estrogen may have a protective role in minimizing glial cell apoptosis in neurological diseases such as demyelinating disease or central nervous system trauma.

Inhibition of tumour growth and inflammation by consumption of tea.

The antitumour effect of tea was evaluated in the 3-methylcholanthrene (3-MC) induced solid tumour model in mice. Both black and green tea inhibited tumour growth and prevented metastasis. Histopathological study showed that tea treatment was able to reduce malignancy. Superoxide dismutase (SOD), a free radical scavenger, was found to be significantly increased in the serum of mice administered tea. Moreover, tea extracts were able to reduce the level of thiobarbituric acid reactive substance (TBARS) in the sera of mice. Tea extracts (both black and green) also showed antiinflammatory activity in the carrageenan-induced paw oedema model in the rat.