title: Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo.
abstract: Recently, several studies have shown that piperlongumine (PL) can selectively kill cancer cells by targeting reactive oxygen species (ROS). However, the potential therapeutic effects and detailed mechanism of PL in gastric cancer are still not clear. In the current report, we found that PL significantly suppressed gastric cancer both in vitro and in vivo. PL obviously increased ROS generation in gastric cancer cells. Anti-oxidant glutathione (GSH) and N-acetyl-L-cysteine (NAC) can abrogate PL-induced gastric cancer cell death and proliferation inhibition. GADD45α was induced in PL-treated cancer cells and led to G2/M phase arrest, whereas genetic depletion of GADD45α by small interfering RNAs (siRNAs) could partly reverse PL-induced cell cycle arrest in gastric cancer cells. Interestingly, we also found that PL treatment decreased the expression of telomerase reverse transcriptase (TERT) gene, which plays an essential role in cancer initiation and progression. Our findings thus revealed a potential anti-tumor effect of PL on gastric cancer cells and may have therapeutic implications.
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Longyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Duan
authors.affiliation: Department of Laboratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. zouxiaoping795@hotmail.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004148:Dioxolanes / Q000494:pharmacology* / Q000627:therapeutic use; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D014410:Tumor Stem Cell Assay; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000097642:GADD45 Proteins; D010881:Piperidones
chemical_list: D000111:Acetylcysteine; D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D004148:Dioxolanes; D005978:Glutathione; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D019098:Telomerase; D051636:X-Linked Inhibitor of Apoptosis Protein; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C494086:STAT3 protein, human; C496866:XIAP protein, human; C509186:TERT protein, human; C498077:piperlongumine; D010881:Piperidones
keywords: CHOP; GADD45α; Gastric cancer; Piperlongumine; ROS; STAT3; TERT