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Role of Oxidation-Triggered Activation of JNK And p38 MAPK in Black Tea Polyphenols Induced Apoptotic Death of A375 Cells

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Title 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
 
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.
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/980/1/13_CS_2009.pdf
Bhattacharya, Udayan and Halder, Babli and Mukhopadhyay, Sibabrata and Giri, Ashok K (2009) 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/980/