title: Hempseed oil induces reactive oxygen species- and C/EBP homologous protein-mediated apoptosis in MH7A human rheumatoid arthritis fibroblast-like synovial cells.
abstract: BACKGROUND
  The medicinal efficacy of hempseed (Cannabis sativa L.), which is rich in polyunsaturated fatty acids, in atopic dermatitis, inflammation, and rheumatoid arthritis (RA) has been suggested for centuries. Hempseed has been used as a treatment for these diseases in Korean and Chinese folk medicine. The aim of the study is to investigate the effects of hempseed oil (HO) on MH7A human RA fibroblast-like synovial cells.
  
  
  METHODS
  MH7A cells were used to study the anti-rheumatoid effects of hempseed (Cannabis sativa L., cv. Cheungsam/Cannabaceae) oil by investigating cell viability, apoptosis, lipid accumulation, oxidative stress, and endoplasmic reticulum (ER) stress-induced apoptosis.
  
  
  RESULTS
  HO treatment reduced the survival rate of MH7A cells and promoted apoptotic cell death in a time- and dose-dependent manner. Both lipid accumulation and the level of intracellular reactive oxygen species (ROS) increased in HO-treated MH7A cells. Co-treatment with the antioxidant Tiron effectively abrogated the cytotoxic effects of HO; the ROS level was reduced, cell viability was recovered, and apoptotic cell death was significantly diminished. Moreover, HO-treated cells exhibited increased expression of the major ER stress markers, glucose-regulated protein 78 and C/EBP homologous protein (CHOP). The siRNA-mediated knockdown of CHOP prevented HO-induced apoptosis.
  
  
  CONCLUSIONS
  Our results suggest that HO treatment induced lipid accumulation, ROS production, CHOP expression, and apoptosis in MH7A cells, and that CHOP functions as an anti-rheumatoid factor downstream of HO in MH7A cells.
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Mini
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jaewook
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences & Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea; Korea Hemp Institute, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea; Korea Hemp Institute, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: kyungho@konkuk.ac.kr.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002188:Cannabis / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010938:Plant Oils / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: D010938:Plant Oils; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP
keywords: Alpha-linolenic acid (PubChem CID: 5280934); Apoptosis; ER stress; Hempseed oil; Linoleic acid (PubChem CID: 5280450); Oleic acid (PubChem CID: 445639); Palmitic acid (PubChem CID: 985); Polyunsaturated fatty acids; Rheumatoid arthritis; Synovial cell