title: 2-O-Methylmagnolol upregulates the long non-coding RNA, GAS5, and enhances apoptosis in skin cancer cells.
abstract: Magnolol, a hydroxylated biphenol compound isolated from the bark of Magnolia officinalis, has been shown to exhibit anti-proliferative effect in various cancer cells, including skin cancer cells. Methoxylation of magnolol appears to improve its anti-inflammatory activity, yet the effect of this modification on the agent's antitumor activity remains unknown. In this work, we report that 2-O-methylmagnolol (MM1) displays improved antitumor activity against skin cancer cells compared to magnolol both in vitro and in vivo. The increased antitumor activity of MM1 appears to correlate with its increased ability to induce apoptosis. DNA microarray and network pathway analyses suggest that MM1 affects certain key factors involved in regulating apoptosis and programmed cell death. Interestingly, the level of the long non-coding (lnc) RNA of growth arrest-specific 5 (GAS5) was increased in MM1-treated cells, and inhibition of lncRNA GAS5 inhibited MM1-induced apoptosis. Conversely, overexpression of lncRNA GAS5 inhibited cell proliferation and promoted cell apoptosis in skin cancer cells. The expression of lncRNA GAS5 in the skin cancer tissues was found to be lower than that in the adjacent normal tissues in a majority of patients. Taken together, our findings suggest that MM1 has improved antitumor activity in skin cancer cells, and that this is due, at least in part, to the upregulation of lncRNA GAS5 and the enhancement of apoptosis.
authors.affiliation: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan 333, Taiwan.|Tissue Bank, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Tong-Hong
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Chieh-Wen
authors.initials: CW
authors.lastname: Chan
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
authors.affiliation: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Shih
authors.affiliation: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Tissue Bank, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan.|Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Tzu-Chien V
authors.initials: TV
authors.lastname: Wang
authors.affiliation: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan 333, Taiwan.|Tissue Bank, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C561567:GAS5 long non-coding RNA, human; D007093:Imidazoles; C512489:MM1 compound; D011759:Pyrrolidines; D062085:RNA, Long Noncoding