6-Shogaol (Alkanone from Ginger) Induces Apoptotic Cell Death of Human Hepatoma p53 Mutant Mahlavu Subline via an Oxidative Stress-Mediated Caspase-Dependent Mechanism
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- 作者：Chung-Yi Chen ; Tsan-Zon Liu ; Yi-Wen Liu ; Wei-Chang Tseng ; Ray H. Liu ; Fung-Jou Lu ; Yu-Shan Lin ; Shih-Hsien Kuo ; Ching-Hsein Chen
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2007
- 出版时间：February 7, 2007
- 年：2007
- 卷：55
- 期：3
- 页码：948 - 954
- 全文大小：662K
- 年卷期：v.55,no.3(February 7, 2007)
- ISSN：1520-5118
文摘
Mahlavu cells, poorly differentiated and p53 mutants of a human hepatoma subline, are known to behighly refractory to a number of chemotherapeutic agents and radiotherapy due to their highexpressions of multidrug resistance gene-1 (MDR-1) and Bcl-2 proteins. Thus, it is desirable to searchfor an alternative strategy for effective eradication of this type of cancer cells. We present evidencehere for the first time that 6-shogaol (6-SG), an alkanone isolated from the rhizomes of ginger, caneffectively 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 aninitial overproduction of reactive oxygen species (ROS) followed by a severe depletion of intracellularglutathione (GSH) contents. Both events consequently entailed a significant drop in mitochondrialtransmembrane potential (
m), which ultimately activated the activities of caspases 3/7 resulting inthe DNA fragmentation. Interestingly, we also found that N-acetylcysteine (NAC), an antioxidant anda precursor of GSH biosynthesis, could offer a near complete protection of apoptotic cell death exertedby 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 cyclosporinA (an mitochondrial permeability transition opening inhibitor) could only partially protect these cellsfrom 6-SG-induced apoptosis. Taking these data into consideration, it is obvious that GSH depletionis 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 cellsby using a natural consistent isolated form of ginger. These data also provide evidence to reaffirmthe notion that consumption of certain foodstuffs can be beneficial to health because some of theconstituents contained in them may be anticarcinogenic.
m), which ultimately activated the activities of caspases 3/7 resulting inthe DNA fragmentation. Interestingly, we also found that N-acetylcysteine (NAC), an antioxidant anda precursor of GSH biosynthesis, could offer a near complete protection of apoptotic cell death exertedby 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 cyclosporinA (an mitochondrial permeability transition opening inhibitor) could only partially protect these cellsfrom 6-SG-induced apoptosis. Taking these data into consideration, it is obvious that GSH depletionis 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 cellsby using a natural consistent isolated form of ginger. These data also provide evidence to reaffirmthe notion that consumption of certain foodstuffs can be beneficial to health because some of theconstituents contained in them may be anticarcinogenic.