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DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress.
Fitoterapia. 2015 Jun; 103:46-54.F

Abstract

2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin (named DAW22), a sesquiterpene coumarin isolated from the roots of Ferula ferulaeoides (Steud.) Korov., has been reported to bear anti-proliferative activities toward different types of cancer cells. In this study, we demonstrated that DAW22 induced apoptosis in C6 glioma cells. Subsequently, we found that DAW22-induced apoptosis in C6 glioma cells occurred via the mitochondria-mediated and death-receptor pathways. Moreover, we found a massive cytoplasmic vacuolization, a dramatic change of endoplasmic reticulum (ER), up-regulation of CHOP and cleavage of caspase-12, suggesting that DAW22-induced apoptosis is involved in ER stress. In addition, we revealed that DAW22 treatment induced the activation of PERK, ATF6α and IRE1α. We further found that knockdown of CHOP affected DAW22-induced apoptosis, and DAW22-stimulated down-regulation of Bcl-2, caspase-8 activation and PARP cleavage were inhibited. Taken together, these results demonstrate that DAW22 induces apoptosis by ER stress and mitochondrial/death-receptor pathways, which may provide a new clue for exploiting this compound as a potential anti-neoplastic drug in future glioma cancer therapy.

Authors+Show Affiliations

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: profhj@163.com.Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Pharmacy, Shihezi University, Shihezi 832002, China. Electronic address: profwjh@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25776007

Citation

Zhang, Lan, et al. "DAW22, a Natural Sesquiterpene Coumarin Isolated From Ferula Ferulaeoides (Steud.) Korov. That Induces C6 Glioma Cell Apoptosis and Endoplasmic Reticulum (ER) Stress." Fitoterapia, vol. 103, 2015, pp. 46-54.
Zhang L, Tong X, Zhang J, et al. DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress. Fitoterapia. 2015;103:46-54.
Zhang, L., Tong, X., Zhang, J., Huang, J., & Wang, J. (2015). DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress. Fitoterapia, 103, 46-54. https://doi.org/10.1016/j.fitote.2015.03.010
Zhang L, et al. DAW22, a Natural Sesquiterpene Coumarin Isolated From Ferula Ferulaeoides (Steud.) Korov. That Induces C6 Glioma Cell Apoptosis and Endoplasmic Reticulum (ER) Stress. Fitoterapia. 2015;103:46-54. PubMed PMID: 25776007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress. AU - Zhang,Lan, AU - Tong,Xupeng, AU - Zhang,Jin, AU - Huang,Jian, AU - Wang,Jinhui, Y1 - 2015/03/14/ PY - 2015/02/25/received PY - 2015/03/08/revised PY - 2015/03/09/accepted PY - 2015/3/18/entrez PY - 2015/3/18/pubmed PY - 2015/9/19/medline KW - Apoptosis KW - C6 glioma cell KW - DAW22 KW - Endoplasmic reticulum (ER) stress KW - Ferula ferulaeoides (Steud.) Korov. SP - 46 EP - 54 JF - Fitoterapia JO - Fitoterapia VL - 103 N2 - 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin (named DAW22), a sesquiterpene coumarin isolated from the roots of Ferula ferulaeoides (Steud.) Korov., has been reported to bear anti-proliferative activities toward different types of cancer cells. In this study, we demonstrated that DAW22 induced apoptosis in C6 glioma cells. Subsequently, we found that DAW22-induced apoptosis in C6 glioma cells occurred via the mitochondria-mediated and death-receptor pathways. Moreover, we found a massive cytoplasmic vacuolization, a dramatic change of endoplasmic reticulum (ER), up-regulation of CHOP and cleavage of caspase-12, suggesting that DAW22-induced apoptosis is involved in ER stress. In addition, we revealed that DAW22 treatment induced the activation of PERK, ATF6α and IRE1α. We further found that knockdown of CHOP affected DAW22-induced apoptosis, and DAW22-stimulated down-regulation of Bcl-2, caspase-8 activation and PARP cleavage were inhibited. Taken together, these results demonstrate that DAW22 induces apoptosis by ER stress and mitochondrial/death-receptor pathways, which may provide a new clue for exploiting this compound as a potential anti-neoplastic drug in future glioma cancer therapy. SN - 1873-6971 UR - https://www.unboundmedicine.com/medline/citation/25776007/DAW22_a_natural_sesquiterpene_coumarin_isolated_from_Ferula_ferulaeoides__Steud___Korov__that_induces_C6_glioma_cell_apoptosis_and_endoplasmic_reticulum__ER__stress_ DB - PRIME DP - Unbound Medicine ER -