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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2018-03-01
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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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