miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells

Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechan...

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Main Authors: Jin Ah Cha, Hyo-Sook Song, Beomku Kang, Moon Nyeo Park, Kyoung Sun Park, Sung-Hoon Kim, Bum-Sang Shim, Bonglee Kim
Format: Article
Language:English
Published: MDPI AG 2018-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/19/3/865
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author Jin Ah Cha
Hyo-Sook Song
Beomku Kang
Moon Nyeo Park
Kyoung Sun Park
Sung-Hoon Kim
Bum-Sang Shim
Bonglee Kim
author_facet Jin Ah Cha
Hyo-Sook Song
Beomku Kang
Moon Nyeo Park
Kyoung Sun Park
Sung-Hoon Kim
Bum-Sang Shim
Bonglee Kim
author_sort Jin Ah Cha
collection DOAJ
description Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). COM also cleaved poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner in both cells. Also, reactive oxygen species (ROS) generation was elevated by COM treatment. Conversely, the apoptotic effect of COM treatment was blocked by N-acetyl-l-cysteine (NAC) pretreatment. Also, the pro-survival miRNA, miR-211 was decreased by COM treatment in U937 and U266 cells. miR-211 mimic attenuated COM-induced apoptosis. Taken together, these results support the scientific evidence that COM induces apoptosis via ROS generation/CHOP activation and miR-211 suppression in U937 and U266 cells.
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spelling doaj.art-a9fcbe935fe34ca6a6dfe473dbd6eea92022-12-22T02:48:42ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-03-0119386510.3390/ijms19030865ijms19030865miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 CellsJin Ah Cha0Hyo-Sook Song1Beomku Kang2Moon Nyeo Park3Kyoung Sun Park4Sung-Hoon Kim5Bum-Sang Shim6Bonglee Kim7Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Korean Medicine Obstetrics & Gynecology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaDepartment of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, KoreaThough Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). COM also cleaved poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner in both cells. Also, reactive oxygen species (ROS) generation was elevated by COM treatment. Conversely, the apoptotic effect of COM treatment was blocked by N-acetyl-l-cysteine (NAC) pretreatment. Also, the pro-survival miRNA, miR-211 was decreased by COM treatment in U937 and U266 cells. miR-211 mimic attenuated COM-induced apoptosis. Taken together, these results support the scientific evidence that COM induces apoptosis via ROS generation/CHOP activation and miR-211 suppression in U937 and U266 cells.http://www.mdpi.com/1422-0067/19/3/865Cnidium officinale Makinoendoplasmic reticulum stressC/EBP homologous proteinreactive oxygen speciesmiR-211
spellingShingle Jin Ah Cha
Hyo-Sook Song
Beomku Kang
Moon Nyeo Park
Kyoung Sun Park
Sung-Hoon Kim
Bum-Sang Shim
Bonglee Kim
miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
International Journal of Molecular Sciences
Cnidium officinale Makino
endoplasmic reticulum stress
C/EBP homologous protein
reactive oxygen species
miR-211
title miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
title_full miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
title_fullStr miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
title_full_unstemmed miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
title_short miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells
title_sort mir 211 plays a critical role in cnidium officinale makino extract induced ros er stress mediated apoptosis in u937 and u266 cells
topic Cnidium officinale Makino
endoplasmic reticulum stress
C/EBP homologous protein
reactive oxygen species
miR-211
url http://www.mdpi.com/1422-0067/19/3/865
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