Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway

Cancer ◽  
2005 ◽  
Vol 104 (4) ◽  
pp. 879-890 ◽  
Author(s):  
Doris R. Siwak ◽  
Shishir Shishodia ◽  
Bharat B. Aggarwal ◽  
Razelle Kurzrock
Keyword(s):  
Protein Kinase ◽  
Nuclear Factor Κb ◽  
Melanoma Cells ◽  
Akt Pathway ◽  
Nuclear Factor ◽  
Iκb Kinase ◽  
Extracellular Signal ◽  
Kinase Pathway

scholarly journals ATM and the Catalytic Subunit of DNA-Dependent Protein Kinase Activate NF-κB through a Common MEK/Extracellular Signal-Regulated Kinase/p90rsk Signaling Pathway in Response to Distinct Forms of DNA Damage

2004 ◽  
Vol 24 (5) ◽  
pp. 1823-1835 ◽  
Author(s):  
Ganesh R. Panta ◽  
Swayamjot Kaur ◽  
Lakita G. Cavin ◽  
Maria L. Cortés ◽  
Frank Mercurio ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Nuclear Factor Κb ◽  
Catalytic Subunit ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Protein Kinase ◽  
Iκb Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Dependent Protein

ABSTRACT We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) signaling that results in nuclear factor κB (NF-κB) activation and chemoresistance in response to DNA damage. We show that the anthracycline doxorubicin (DOX) and its congener N-benzyladriamycin (AD 288) selectively activate ATM and DNA-PK, respectively. Both ATM and DNA-PK promote sequential activation of the mitogen-activated protein kinase (MAPK)/p90 rsk signaling cascade in a p53-independent fashion. In turn, p90 rsk interacts with the IκB kinase 2 (IKK-2) catalytic subunit of IKK, thereby inducing NF-κB activity and cell survival. Collectively, our findings suggest that distinct members of the phosphatidylinositol kinase family activate a common prosurvival MAPK/IKK/NF-κB pathway that opposes the apoptotic response following DNA damage.

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