Methylprednisolone and indomethacin inhibit oxidative stress mediated apoptosis in rat C6 glioblastoma cells.
Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy, and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin (IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen peroxide (H(2)O(2)). Exposure of C6 cells to 1 mM H(2)O(2) for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2 at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa alpha-spectrin breakdown product. Immunofluorescent and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well. Treatment of cells with 1 microM MP or 10 microM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 microM MP or 10 microM IM significantly inhibited H(2)O(2) mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal, may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress.
Das
Arabinda
A
Department of Neurosciences, Medical University of South Carolina (MUSC), 96 Jonathan Lucas Street, Suite 323K, P.O. Box 250606, Charleston, SC 29425, USA.
Banik
Naren L
NL
Ray
Swapan K
SK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000096:biosynthesis; D053148:Caspase 3 / Q000502:physiology; D005909:Glioblastoma / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051381:Rats; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002154:Calpain; D053148:Caspase 3; D008775:Methylprednisolone; D007213:Indomethacin