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.