Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation.
BACKGROUND
Piroxicam (Px) belongs to the oxicam group of the non-steroidal anti-inflammatory drugs (NSAIDs) and have been shown to exert chemopreventive and chemotherapeutic effects in animal models and cultured animal cells. However, little is known about the mode of action of Px and its cellular targets.


METHODS
We explored the role of Px, in triggering apoptosis and examined the involvement of upstream cellular mechanisms in apoptosis induction by Px.


CONCLUSIONS
Our studies with human breast cancer cells MCF-7 show that Px induces reactive oxygen species (ROS) generation along with apoptotic cell death. ROS release lead to Akt activation. On evaluation it became evident that ROS mediated apoptosis induction was due to Akt activation (hyper phosphorylation). Silencing the expression of Akt using siRNA and a specific Akt inhibitor, triciribine further confirmed the findings. However Px failed to cause ROS generation, cell death or Akt phosphorylation in another human breast cancer cells MDA-MB-231 which is estrogen receptor negative and more aggressive compared to MCF-7 cells. This suggests that Px has cell type specific effects. Thus we revealed for the first time that Px can induce apoptosis by ROS mediated Akt hyperphosphorylation/activation.
Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan nagar, Kolkata 700064, India.
Neha
N
Rai
Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhan nagar, Kolkata 700064, India.
Munna
M
Sarkar
Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan nagar, Kolkata 700064, India; Department of Biotechnology and ISERC, Visva Bharati University, Santiniketan, India. Electronic address: sanghamitra.raha@visva-bharati.ac.in.
Sanghamitra
S
Raha
D000111:Acetylcysteine / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010766:Phosphorylation; D010894:Piroxicam / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012263:Ribonucleosides; D010894:Piroxicam; C023764:triciribine; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D000111:Acetylcysteine
Akt; Apoptosis; MCF-7; Piroxicam; Reactive oxygen species (ROS)