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Int J Mol Sci. 2018 Mar 15;19(3). pii: E865. doi: 10.3390/ijms19030865.

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

Author information

1
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. nicesh89@khu.ac.kr.
2
Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. shs331@khu.ac.kr.
3
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. beomkukang@khu.ac.kr.
4
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. mnpark@khu.ac.kr.
5
Department of Korean Medicine Obstetrics & Gynecology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. lovepks@khnmc.or.kr.
6
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. sungkim7@khu.ac.kr.
7
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. eshimbs@khu.ac.kr.
8
Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. bongleekim@khu.ac.kr.
9
Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. bongleekim@khu.ac.kr.

Abstract

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.

KEYWORDS:

C/EBP homologous protein; Cnidium officinale Makino; endoplasmic reticulum stress; miR-211; reactive oxygen species

PMID:
29543750
PMCID:
PMC5877726
DOI:
10.3390/ijms19030865
[Indexed for MEDLINE]
Free PMC Article

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