Mahlavu cells, poorly differentiated and p53 mutants of a human hepatoma subline, are known to be highly refractory to a number of chemotherapeutic agents and radiotherapy due to their high expressions of multidrug resistance gene-1 (MDR-1) and Bcl-2 proteins. Thus, it is desirable to search for an alternative strategy for effective eradication of this type of cancer cells. We present evidence here for the first time that 6-shogaol (6-SG), an alkanone isolated from the rhizomes of ginger, can effectively induce apoptotic cell death of Mahlavu cells via an oxidative stress-mediated caspase-dependent mechanism. The cascade of events in 6-SG-induced apoptosis of these cells involved an initial overproduction of reactive oxygen species (ROS) followed by a severe depletion of intracellular glutathione (GSH) contents. Both events consequently entailed a significant drop in mitochondrial transmembrane potential (DeltaPsim), which ultimately activated the activities of caspases 3/7 resulting in the DNA fragmentation. Interestingly, we also found that N-acetylcysteine (NAC), an antioxidant and a precursor of GSH biosynthesis, could offer a near complete protection of apoptotic cell death exerted by 6-SG. Similarly, exogenously added GSH could also provide protection with an equal efficacy. However, it was paradoxical that both Boc-Asp(OMe)-fmk (a broad caspases inhibitor) and cyclosporin A (an mitochondrial permeability transition opening inhibitor) could only partially protect these cells from 6-SG-induced apoptosis. Taking these data into consideration, it is obvious that GSH depletion is the major contributing factor in arbitrating 6-SG-induced apoptosis of Mahlavu cells. In conclusion, we provide here a novel modality that can help to eradicate a p53 mutant of human hepatoma cells by using a natural consistent isolated form of ginger. These data also provide evidence to reaffirm the notion that consumption of certain foodstuffs can be beneficial to health because some of the constituents contained in them may be anticarcinogenic.
In the present study, the concentrations of copper, iron, zinc, and malondialdehyde in human seminal plasma were measured and correlated with the sperm count and motility in human semen. Copper, iron, and zinc were analyzed by atomic absorption spectrometry, whereas malondialdehyde was measured by high-performance liquid chromatography. The malondialdehyde concentrations in asthenospermia and oligoasthenospermia were significantly higher than in normospermia. Copper and iron levels were higher in asthenospermia, whereas the zinc concentrations in both oligospermia and asthenospermia were lower than in normal controls. A negative correlation (r = -0.28, p < 0.05) between the malondialdehyde concentration and sperm motility was observed in the abnormal groups. There was no association among copper, iron, zinc, and malondialdehyde in seminal plasma. We concluded that changes in trace elements may be related to sperm quality and that lipid peroxidation, although it is not promoted in the seminal plasma by copper or iron or ameliorated by zinc, may be involved in the loss of sperm motility.
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