| Institution: | 1. University of North Carolina Lineberger Comprehensive Cancer Center, Advanced Cellular Therapeutics Facility, Chapel Hill, North Carolina, USA. ISCT North America, Past Regional Vice President 2012–2014;2. Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. Chair, ISCT NA LRA Committee, 2014–2016 and Co-Editor of the Telegraft;3. St Jude Children''s Research Hospital, Memphis, Tennessee, USA. ISCT Past Co-Chair, NA LRA Committee 2011–2014. ISCT North America, Regional Vice President 2014–2016;4. Division of Hematology, Cell Therapy Laboratory, The Ohio State University, Columbus, Ohio, USA. ISCT Global Secretary, 2013–2016 and Editor in Chief of Telegraft;1. Division of Hematology, Cell Therapy Laboratory, The Ohio State University, Columbus, Ohio, USA, International Society for Cellular Therapy (ISCT) Global Secretary 2013–2016, Editor in Chief of Telegraft;2. University of Minnesota Center for Bioethics and School of Public Health, Minneapolis, Minnesota, USA, Member at Large of the ISCT Presidential Task Force on the Use of Unproven Cellular Therapies;3. School of Public Policy, Georgia Institute of Technology, Atlanta, Georgia, USA, Member at large of the ISCT Presidential Task Force on the Use of Unproven Cellular Therapies |
| Abstract: | Buforin IIb, a novel cell-penetrating anticancer peptide derived from histone H2A, has been reported to induce mitochondria-dependent apoptosis in tumor cells. However, increasing evidence suggests that endoplasmic reticulum and mitochondria cooperate to signal cell death. In this study, we investigated the mechanism of buforin IIb-induced apoptosis in human cervical carcinoma HeLa cells by focusing on ER stress-mediated mitochondrial membrane permeabilization. Two-dimensional PAGE coupled with MALDI-TOF and western blot analysis showed that buforin IIb treatment of HeLa cells resulted in upregulation of ER stress proteins. PBA (ER stress inhibitor) and BAPTA/AM (Ca2+ chelator) pretreatment rescued viability of buforin IIb-treated cells through abolishing phosphorylation of SAPK/JNK and p38 MAPK. SP600125 (SAPK/JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated down-regulation of Bcl-xL/Bcl-2, mitochondrial translocation of Bax, and cytochrome c release from mitochondria. Taken together, our data suggest that the ER stress pathway has an important role in the buforin IIb-induced apoptosis in HeLa cells. |
