title: Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway.
abstract: Lung cancer is the most common cause of cancer-related mortality in the US as well as other regions of the world. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major components of Curcuma longa L. It has been reported that curcumin inhibits the growth of various types of cancer cells in vitro and in vivo. However, the mechanisms involved in the inhibition of cell growth and induced apoptosis by DMC in human lung cancer cells remain unclear. In the present study, we investigated the effect of DMC on cell death via the induction of apoptosis in NCI-H460 human lung cancer cells. Flow cytometric assay was used to examine the total percentage of viable cells, the population of cells in the sub-G1 phase of the cell cycle, the level of reactive oxygen species (ROS), Ca²⁺ production, mitochondrial membrane potential (ΔΨm) and caspase activity. Western blotting was used to examine the changes in the expression of cell cycle- and apoptosis-associated proteins. Confocal microscopy was used to examine the translocation of apoptosis-associated proteins. The results indicated that DMC significantly induced cell morphological changes and decreased the percentage of viable NCI-H460 cells and DMC induced apoptosis based on the cell distribution in the sub-G1 phase. Moreover, DMC promoted ROS and Ca²⁺ production and decreased the level of ΔΨm and promoted the activities of caspase-3, -8 and -9. The Western blotting results showed that DMC promoted the expression of AIF, Endo G and PARP. The levels of Fas ligand (Fas L) and Fas were also upregulated. Furthermore, DMC promoted expression of ER stress-associated proteins such as GRP78, GADD153, IRE1β, ATF-6α, ATF-6β and caspase-4. Based on the findings, we suggest that DMC may be used as a novel anticancer agent for the treatment of lung cancer in the future.
authors: Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Yang-Ching
authors: YC
authors: Ko
authors: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Jin-Cherng
authors: JC
authors: Lien
authors: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Hsin-Chung
authors: HC
authors: Liu
authors: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Shu-Chun
authors: SC
authors: Hsu
authors: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
authors: Bin-Chuan
authors: BC
authors: Ji
authors: Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, R.O.C.
authors: Mei-Due
authors: MD
authors: Yang
authors: Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Wu-Huei
authors: WH
authors: Hsu
authors: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D036381:Diarylheptanoids; D000091342:Endoplasmic Reticulum Chaperone BiP; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D036381:Diarylheptanoids; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species; D020169:Caspases; D003474:Curcumin; D002118:Calcium; C050229:demethoxycurcumin