title: Curcumin analog L48H37 induces apoptosis through ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells.
abstract: Lung cancer is the leading cause of cancer-related deaths. Curcumin is a well-known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously, we reported that L48H37, a novel analog of curcumin with higher bioavailability, ameliorated LPS-induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells. Our results show that L48H37 decreases lung cancer cell growth and colony formation. These alterations were mediated through induction of G2/M cell cycle arrest and apoptosis in lung cancer cells. After L48H37 treatment, ER stress-related proteins were increased, and the expression of p-STAT3 was decreased in a dose-dependent manner. L48H37 also induced the accumulation of ROS in lung cancer cells, and pretreatment with NAC could fully reverse L48H37-induced reactive oxygen species (ROS) increase. Blocking ROS was able to reverse L48H37-induced endoplasmic reticulum (ER) stress, cell cycle arrest, and apoptosis. Finally, we show that L48H37 inhibits the growth of lung cancer xenografts without exhibiting toxicity. Treatment of mice bearing human lung cancer xenografts with L48H37 was also associated with indices of ER stress activation. In summary, our results provide evidence for a novel anti-tumor candidate for the treatment of lung cancer.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Miaoshan
authors.initials: M
authors.lastname: Shen
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Ying
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Dai
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Weishan
authors.initials: W
authors.lastname: Zhuge
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Guang
authors.identifier: 0000-0002-8278-849X
authors.initials: G
authors.lastname: Liang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.|College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D003474:Curcumin
keywords: ER stress; ROS; STAT3; curcumin analog; lung cancer