TY - JOUR T1 - Characterizing the Sphingomyelinase Pathway Triggered by PRIMA-1 Derivatives in Lung Cancer Cells with Differing p53 Status JF - Anticancer Research JO - Anticancer Res SP - 3271 LP - 3283 VL - 34 IS - 7 AU - EROICA SOANS AU - SUSAN C. EVANS AU - CYNTHIA CIPOLLA AU - ELROY FERNANDES Y1 - 2014/07/01 UR - http://ar.iiarjournals.org/content/34/7/3271.abstract N2 - Background/Aim: Derivatives of PRIMA-1 compound, 8a and 8b have been shown to increase cytotoxicity in lung cancer cells through sphingomyelinase pathways in IR and 8a or 8b co-treated lung cancer cells. The goal of the present study was to further elaborate the molecular mechanism of 8a- or 8b-treated lung cancer cells in order to understand their potential as anti-cancer drugs. Materials and Methods: Biochemical assays, western blot, flow cytometry and gene array analyses were employed to distinguish these mechanisms. Results: Herein we demonstrated that 8a and 8b cause apoptosis with S-phase arrest in lung cancer cells by activating neutral sphingomyelinase with ceramide production. 8a induces expression of TNF family genes while 8b induces p53-mediated apoptosis genes. Protein analysis shows an increased expression in caspase 8, bcl-2, bax, caspase 9 and cytochrome c. Conclusion: PRIMA-1 derivatives provoke cytotoxicity in lung cancer cells mainly through the neutral sphingomyelinase-dependent apoptosis pathway. ER -