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Blackwell Publishing Asia Role of Oxidation-Triggered Activation of JNK and p38 MAPK in black tea Polyphenols Induced Apoptotic Death of A375 Cells

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Blackwell Publishing Asia Role of Oxidation-Triggered Activation of JNK and p38 MAPK in black tea Polyphenols Induced Apoptotic Death of A375 Cells
 
Creator Bhattacharya, Udayan
Halder, Babli
Mukhopadhyay, Sibabrata
Giri, Ashok K
 
Subject Chemistry
Molecular & Human Genetics
 
Description Theaflavins (TF) and thearubigins (TR) are the major polyphenols of black tea. Our previous study revealed that TF- and TR-induced apoptosis of human malignant melanoma cells (A375) is executed via a mitochondria-mediated pathway. In our present study we observed the role of the three most important MAPK (ERK, JNK, and p38) in TF- and TR-induced apoptosis. TF and TR treatment of A375 cells led to sustained activation of JNK and p38 MAPK but not ERK, suggesting that JNK and p38 are the effector molecules in this polyphenol-induced cell death. This idea was further supported by subsequent studies in which JNK and p38 activation was inhibited by specific inhibitors. Significant inhibition was found in TF- and TRtreated A375 cell death pretreated with JNK- or p38-specific inhibitors only. Further, we have found that TF and TR treatment induces a time-dependent increase in intracellular reactive oxygen species generation in A375 cells. Interestingly, treatment with the antioxidant N-acetyl cystein inhibits TF- and TR-induced JNK and p38 activation as well as induction of cell death in A375 cells. We also provide evidence demonstrating the critical role of apoptosis signal-regulating kinase 1 in TF- and TR-induced apoptosis in A375 cells. Taken together our results strongly suggest that TF and TR induce apoptotic death of A375 cells through apoptosis signalregulating kinase 1, MAPK kinase, and the JNK–p38 cascade, which is triggered by N-acetyl cystein intracellular oxidative stress. (Cancer Sci 2009; 100: 1971–1978)
 
Publisher Oxford University Press
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/137/1/CANCER_SCIENCE%2C100(10)%2C1971%2D1978_%2C2009[22].pdf
Bhattacharya, Udayan and Halder, Babli and Mukhopadhyay, Sibabrata and Giri, Ashok K (2009) Blackwell Publishing Asia Role of Oxidation-Triggered Activation of JNK and p38 MAPK in black tea Polyphenols Induced Apoptotic Death of A375 Cells. Cancer Science, 100 (10). pp. 1971-1978.
 
Relation http://dx.doi.org/10.1111/j.1349-7006.2009.01251.x
http://www.eprints.iicb.res.in/137/