PMID- 31787236 OWN - NLM STAT- MEDLINE DCOM- 20200831 LR - 20200831 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 522 IP - 3 DP - 2020 Feb 12 TI - Protective role of c-Jun NH(2)-terminal kinase-associated leucine zipper protein (JLP) in curcumin-induced cancer cell death. PG - 697-703 LID - S0006-291X(19)32282-X [pii] LID - 10.1016/j.bbrc.2019.11.154 [doi] AB - Previous studies have established the antitumor activity of curcumin, a major component of turmeric. Increasing evidence indicates that curcumin induces autophagy, the activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathways, and reactive oxygen species (ROS)-mediated cell death. The c-Jun NH(2)-terminal kinase (JNK)-associated leucine zipper protein (JLP), a scaffold protein for MAPK signaling pathways, has been identified as a candidate biomarker for cancer. In this study, we explored the role of JLP in curcumin-induced cancer cell death. We found that JLP knockdown (KD) increases cell death and intracellular ROS levels. Furthermore, JLP KD impaired lysosomal accumulation around perinuclear regions, which led to the inhibition of autophagosome-lysosome fusion, and attenuated p38 MAPK activation in curcumin-treated cells. The decreases in cell viability and p38 MAPK activation were reversed by expressing wild-type JLP but not a JLP mutant lacking the p38 MAPK-binding domain. In addition, the inactivation of a key gene involved in autophagy increased sensitivity to curcumin-induced cell death. Together, these results suggest that JLP mediates the induction of autophagy by regulating lysosome positioning and p38 MAPK signaling, indicating an overall protective role in curcumin-induced ROS-mediated cancer cell death. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Boldbaatar, Jambaldorj AU - Boldbaatar J AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Gunarta, I Ketut AU - Gunarta IK AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Suzuki, Ryusuke AU - Suzuki R AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Erdenebaatar, Purev AU - Erdenebaatar P AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Davaakhuu, Gantulga AU - Davaakhuu G AD - Laboratory of Molecular Biology, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia. FAU - Hohjoh, Hirohiko AU - Hohjoh H AD - Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan. FAU - Yoshioka, Katsuji AU - Yoshioka K AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. Electronic address: katsuji@staff.kanazawa-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191128 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antineoplastic Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (SPAG9 protein, human) RN - IT942ZTH98 (Curcumin) SB - IM MH - Adaptor Proteins, Signal Transducing/*metabolism MH - Antineoplastic Agents/*pharmacology MH - Autophagy/drug effects MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Curcumin/*pharmacology MH - Humans MH - Neoplasms/*drug therapy/metabolism MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Autophagy OT - Cell death OT - Lysosome OT - MAP kinase OT - ROS EDAT- 2019/12/04 06:00 MHDA- 2020/09/01 06:00 CRDT- 2019/12/03 06:00 PHST- 2019/11/13 00:00 [received] PHST- 2019/11/22 00:00 [accepted] PHST- 2019/12/04 06:00 [pubmed] PHST- 2020/09/01 06:00 [medline] PHST- 2019/12/03 06:00 [entrez] AID - S0006-291X(19)32282-X [pii] AID - 10.1016/j.bbrc.2019.11.154 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2020 Feb 12;522(3):697-703. doi: 10.1016/j.bbrc.2019.11.154. Epub 2019 Nov 28.