title: Induction of apoptosis by curcumin in murine myelomonocytic leukemia WEHI-3 cells is mediated via endoplasmic reticulum stress and mitochondria-dependent pathways.
abstract: Curcumin, derived from the food flavoring spice turmeric (Curcuma longa), has been shown to exhibit anticancer activities and induce apoptosis in many types of cancer cell lines. In our previous study, curcumin was able to inhibit murine myelomonocytic leukemia WEHI-3 cells in vivo. However, there is no report addressing the cytotoxic responses and the mechanisms underlying curcumin-induced apoptotic cell death in WEHI-3 cells. Therefore, we hypothesized that that curcumin affected WEHI-3 cells and triggered cell death through apoptotic signaling pathways. The effects of curcumin on WEHI-3 cells were investigated by using flow cytometric analysis, comet assay, confocal laser microscopy and Western blotting. In this study, we found that curcumin induced apoptosis in WEHI-3 cells in a dose-dependent (5-20 μM) manner. Interestingly, curcumin enhanced the level of the antiapoptotic protein Bcl-2 which might show that curcumin-induced apoptosis is done through the ER stress signaling pathways based on the increase of CIEBP homologous protein (CHOP), activating transcription factor 6 (ATF-6), inositol-requiring enzyme 1 (IRE1), and caspase-12 in WEHI-3 cells. Moreover, curcumin increased the reactive oxygen species (ROS) production and cytosolic Ca²⁺ release, and induced DNA damage, but decreased the level of mitochondrial membrane potential (ΔΨm ) in WEHI-3 cells. In conclusion, curcumin-induced apoptosis occurs through the ROS-affected, mitochondria-mediated and ER stress-dependent pathways. The evaluation of curcumin as a potential therapeutic agent for treatment of leukemia seems warranted.
authors.affiliation: Department of Nursing, ST. Mary's Medicine Nursing and Management College, Yilan 266, Taiwan.
authors.forename: An-Cheng
authors.initials: AC
authors.lastname: Huang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chang
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Bin-Chuan
authors.initials: BC
authors.lastname: Ji
authors.forename: Tsung-Ping
authors.initials: TP
authors.lastname: Lin
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
authors.forename: Su-Peng
authors.initials: SP
authors.lastname: Yeh
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D007951:Leukemia, Myeloid; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D020169:Caspases; D003474:Curcumin; D002118:Calcium