HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

6-shogaol (alkanone from ginger) induces apoptotic cell death of human hepatoma p53 mutant Mahlavu subline via an oxidative stress-mediated caspase-dependent mechanism.

Abstract
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.
AuthorsChung-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
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 55 Issue 3 Pg. 948-54 (Feb 07 2007) ISSN: 0021-8561 [Print] United States
PMID17263498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Catechols
  • Plant Extracts
  • Reactive Oxygen Species
  • shogaol
  • Caspases
Topics
  • Apoptosis (drug effects)
  • Carcinoma, Hepatocellular (pathology)
  • Caspases (metabolism)
  • Catechols (pharmacology)
  • Cell Line, Tumor
  • DNA Damage (drug effects)
  • Ginger (chemistry)
  • Humans
  • Liver Neoplasms (pathology)
  • Mutation
  • Oxidative Stress
  • Plant Extracts
  • Plant Roots (chemistry)
  • Reactive Oxygen Species (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: