Apoptosis Induced by Piroxicam plus Cisplatin Combined Treatment Is Triggered by p21 in Mesothelioma

Abstract

BackgroundMalignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase.Methodology/Principal FindingsWe analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing.Conclusions/SignificancePiroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.

CD44 variant‐dependent redox status regulation in liver fluke‐associated cholangiocarcinoma: A target for cholangiocarcinoma treatment

“…The oxidative stress affects the cellular behavior through intracellular signaling responses such as the MAPK pathways, especially p38 MAPK . It is involved in cell differentiation, apoptosis, and autophagy through the activation of several kinase proteins; for instance, p21 is an important cell cycle inhibitor, resulting in G 1 cell cycle arrest, senescence, and apoptosis . Furthermore, an increase in Atg proteins through p38 MAPK signaling leads to the conversion of LC3‐I to LC3‐II, resulting in autophagy accumulation and cell death …”

“…It is involved in cell differentiation, apoptosis, and autophagy through the activation of several kinase proteins; for instance, p21 is an important cell cycle inhibitor, (8) resulting in G 1 cell cycle arrest, (9) senescence, (10) and apoptosis. (11) Furthermore, an increase in Atg proteins through p38 MAPK signaling leads to the conversion of LC3-I to LC3-II, resulting in autophagy accumulation and cell death. (12) Cholangiocarcinoma is a malignancy of the bile duct epithelial cells, mainly caused by chronic inflammation due to Ov infection in Southeast Asia, especially in northeast Thailand.…”

Malign plevral mezotelyomada ilaç taşıyıcı nanosistemler

“…Uygulanan kombine tedavi sonucunda anti-tümoral etkinin ortaya çıktığı, hem in vivo hemde in vitro da yaşam süresinin uzadığı göste-rilmiştir. Mezotelyoma hücrelerine piroksikam ve sisplatin uygulandığı takdirde hücre döngüsü regülas-yonunda meydana gelen düzensizlik sonucunda apoptozun tetiklendiği gösterilmiştir (80). PLGA (Poly-(D, L-lactic-coglycolic)acid), zamanından önce ilaç degredasyonunu önleyen en önemli polimerdir.…”

Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation

“…Px has been shown to 24 induce apoptosis in human malignant mesothelioma cell line in 25 combination with cisplatin and in human oral squamous cell 26 carcinoma cells (OSCC) in combination with Masitinib, AB1010 27 [6,7]. Preliminary data on the cytotoxic effects of Px on human 28 breast cancer cell lines are available but thorough explorations of 29 the upstream mechanisms have not been done [8].…”

“…G ModelPHAREP 344[1][2][3][4][5][6][7][8][9] Please cite this article in press as:Rai N, et al Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation. Pharmacol Rep (2015), http://dx.doi.org/10.1016/j.pharep.2015.05.012…”