Oxygen-releasing manganese clay hybrid complex triggers p53-mediated cancer cell death in hypoxia.

Hypoxia in tumor microenvironment is responsible for resistance to conventional modes of cancer therapeutics. A manganese-clay hybrid compound MHC was shown to generate molecular oxygen in aqueous solution. In this study we have shown that MHC, in hypoxia, causes cancer cell death, through release of molecular oxygen and via p53-dependent apoptosis. MHC treatment of cells results in depletion of mitochondrial membrane potential and inhibition of ROS production, in a cell-specific manner. In hypoxia, the oxygen from MHC releases cells from S-phase arrest thus causing p53-dependent apoptosis. The induction of apoptosis by MHC is higher in p53 Wt/Wt cells when it is compared with p53 Mt/Mt cells. The released oxygen from MHC triggers apoptosis via p53 activation through its enhanced homo-oligomerization, post-translational modifications and nuclear localization. Thus MHC as a cellular oxygen-releasing compound has high potential as a drug for hypoxic tumor regression.

Berberine in combination with doxorubicin suppresses growth of murine melanoma B16F10 cells in culture and xenograft.

Melanoma is very aggressive and major cause of mortality due to skin cancer. Herein, we studied the anticancer effects of berberine, a plant alkaloid, in combination with doxorubicin on murine melanoma B16F10 cells in vitro and in vivo. This drug combination strongly inhibited cell growth and induced cell death, and caused G2/M arrest in cell cycle together with a decrease in Kip1/p27. Berberine showed stronger inhibitory effect on ERK1/2 phosphorylation as compared to Akt phosphorylation, whereas the combination of the drugs showed greater inhibitory effect on Akt phosphorylation. In murine B16F10 xenograft, cells were implanted into mice and treated with vehicle (methyl cellulose) or berberine (100mg/kg of body weight/day by oral gavage) or doxorubicin (4 mg/kg of body weight/week by intraperitoneal injection) or combination of berberine and doxorubicin. Berberine alone did not show any considerable effect on tumor growth as observed with doxorubicin, however, the combination of the two drugs resulted in a significant and strong decrease in tumor volume (85%, p<0.005) and tumor weight (78%, p<0.05) as compared to control. Immunohistochemical analysis of tumor samples showed that drug combination decreased PCNA-positive cells (82%, p<0.001) and increased cleaved caspase-3 positive cells (3-fold, p<0.05) indicating inhibition of proliferation and an increase in apoptosis, respectively. Overall, our findings suggest that berberine and doxorubicin could be a novel combination to inhibit melanoma tumor growth.

A study of homicidal deaths in Delhi.

A meticulous post-mortem review was undertaken in the department of forensic medicine at the Maulana Azad Medical College (MAMC) to find out trends in homicides during the period 1992-1996. Standard procedures for autopsies and a review of the inquest papers were carried out. Out of 3,886 medico-legal autopsies performed in the department during the said period, only 232 cases (5.9%) were homicidal deaths. The commonest age group of the victims was 21-30 years (38%). Males were victimized three times more often than females. The incidence of crime was slightly more at night than in the daytime, though evenly distributed during the winter and summer seasons. In our series, sharp weapon injuries were the most common type (34.9%) followed by blunt force injuries (15.9%). Defence wounds were present in 35 cases (15%). Violent rage/quarrel was the motive in 61 cases (29%).