title: Buforin IIb induces endoplasmic reticulum stress-mediated apoptosis in HeLa cells.
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 (Ca(2+) 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.
authors.affiliation: Department of Biology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Biology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea.
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Biology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea. Electronic address: juhyun.cho@gnu.kr.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics; D011506:Proteins / Q000008:administration & dosage* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D010455:Peptides; D011506:Proteins; D017382:Reactive Oxygen Species; C097849:buforin II
keywords: Anticancer peptide; Apotosis; Buforin IIb; ER stress; Mitochondrial membrane permeabilization