PRODH/POX-Dependent Celecoxib-Induced Apoptosis in MCF-7 Breast Cancer

Abstract

Celecoxib (Cx), an inhibitor of cyclooxygenase 2, induces apoptosis of cancer cells. However, the mechanism of the chemopreventive effect remains not fully understood. We aimed to investigate the role of PRODH/POX that is involved in the regulation of apoptosis induced by celecoxib. MCF-7 breast cancer cell line and the corresponding MCF-7 cell line with silenced PRODH/POX (MCF-7shPRODH/POX) were used. The effects of Cx on cell viability, proliferation, and cell cycle were evaluated. The expressions of protein markers for apoptosis (Bax, caspase 9, and PARP) and autophagy (Atg5, Beclin 1, and LC3A/B) were investigated by Western immunoblotting. To analyze the proline metabolism, collagen biosynthesis, prolidase activity, proline concentration, and the expression of proline-related proteins were evaluated. The generation of ATP, ROS, and the ratio of NAD+/NADH and NADP+/NADPH were determined to test the effect of Cx on energetic metabolism in breast cancer cells. It has been found that Cx attenuated MCF-7 cell proliferation via arresting the cell cycle. Cx induced apoptosis in MCF-7 breast cancer cells, while in MCF-7shPRODH/POX, autophagy occurred more predominantly. In MCF-7 breast cancer cells, Cx affected proline metabolism through upregulation of proline biosynthesis, PRODH/POX and PYCRs expressions, PEPD activity, and downregulation of collagen biosynthesis. In MCF-7shPRODH/POX clones, these processes, as well as energetic metabolism, were remarkably suppressed. The data for the first time suggest that celecoxib induces apoptosis through upregulation of PRODH/POX in MCF-7 breast cancer cells.

Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis

“…In fact, COX2 is overexpressed in most cancer cells [5]. The postulated antiinflammatory mechanism of the proapoptotic properties of NSAIDs seems to be not the only one, since the cells lacking COX2 also responded to NSAID-induced apoptosis, suggesting a COX2-independent mechanism [9,10,[12][13][14][45][46][47][48].…”

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis

“…Therefore, targeting proline metabolism may be an effective strategy for prevention and treatment of cancers. During the progression of proline metabolism, the ROS production level is decreased, and meanwhile proline and ATP production levels are increased, which finally facilitates tumor metastasis and invasion [ 31 , 32 ]. In the present study, we found that circ_0000705 functioned as a promoter of proline metabolism in ESCC cells by facilitating the proline and ATP production and meanwhile restraining ROS production, suggesting that circ_0000705 may facilitate ESCC progression by promoting proline metabolism.…”

Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing

“…HaCaT cells (seeded on 6-well plates at 2 × 10 5 cells/well) were treated with 50 nM of rhPEPD WT , rhPEPD-G448R, rhPEPD-231delY, and rhPEPD-E412K for 24 h. After incubation, cells were subjected to the protocol as published previously ( Misiura et al, 2021b ). Ethanol-fixed cells were analyzed using an image cytometer NC-3000 (ChemoMetec, Allerod, Denmark).…”