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Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer.
Pharmacol Res 2016; 111:113-125PR

Abstract

Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway.

Authors+Show Affiliations

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX, 77030, USA.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: liuzq@gzucm.edu.cn.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: lllu@gzucm.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

27268146

Citation

Liu, Yuting, et al. "Novel Histone Deacetylase Inhibitors Derived From Magnolia Officinalis Significantly Enhance TRAIL-induced Apoptosis in Non-small Cell Lung Cancer." Pharmacological Research, vol. 111, 2016, pp. 113-125.
Liu Y, Tong Y, Yang X, et al. Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer. Pharmacol Res. 2016;111:113-125.
Liu, Y., Tong, Y., Yang, X., Li, F., Zheng, L., Liu, W., ... Lu, L. (2016). Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer. Pharmacological Research, 111, pp. 113-125. doi:10.1016/j.phrs.2016.05.028.
Liu Y, et al. Novel Histone Deacetylase Inhibitors Derived From Magnolia Officinalis Significantly Enhance TRAIL-induced Apoptosis in Non-small Cell Lung Cancer. Pharmacol Res. 2016;111:113-125. PubMed PMID: 27268146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer. AU - Liu,Yuting, AU - Tong,Yunli, AU - Yang,Xia, AU - Li,Fangyuan, AU - Zheng,Liang, AU - Liu,Wenqin, AU - Wu,Jinjun, AU - Ou,Rilan, AU - Zhang,Guiyu, AU - Hu,Ming, AU - Liu,Zhongqiu, AU - Lu,Linlin, Y1 - 2016/06/03/ PY - 2016/01/18/received PY - 2016/05/24/revised PY - 2016/05/25/accepted PY - 2016/6/9/entrez PY - 2016/6/9/pubmed PY - 2017/12/27/medline KW - Histone deacetylase KW - Honokiol (PubChem CID: 72303) KW - Magnolol KW - Magnolol (PubChem CID: 72300) KW - Non-small cell lung cancer KW - Obovatol (PubChem CID: 100771) KW - Polyphenol mixture KW - TRAIL SP - 113 EP - 125 JF - Pharmacological research JO - Pharmacol. Res. VL - 111 N2 - Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/27268146/Novel_histone_deacetylase_inhibitors_derived_from_Magnolia_officinalis_significantly_enhance_TRAIL_induced_apoptosis_in_non_small_cell_lung_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(16)30050-0 DB - PRIME DP - Unbound Medicine ER -