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Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

DC Field Value Language
dc.contributor.authorYoo, Eunsu-
dc.contributor.authorLee, Jaehak-
dc.contributor.authorLertpatipanpong, Pattawika-
dc.contributor.authorRyu, Junsun-
dc.contributor.authorKim, Chong-Tai-
dc.contributor.authorPark, Eul-Yong-
dc.contributor.authorBaek, Seung Joon-
dc.date.accessioned2020-10-07T06:36:13Z-
dc.date.available2020-10-07T15:37:23Z-
dc.date.issued2020-09-14-
dc.identifier.citationBMC Cancer. 2020 Sep 14;20(1):881ko_KR
dc.identifier.issn1471-2407-
dc.identifier.urihttps://hdl.handle.net/10371/169012-
dc.description.abstractBackground
A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown.

Methods
Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays.

Results
Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity.

Conclusion
In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.		ko_KR
dc.description.sponsorshipThis work was supported by the Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2018R1A2B2002923) to S.J.B. This work was also partially supported by a clinical research grant (NCC1810150) provided by the National Cancer Center to J.R. and S.J.B. The Fig. 7 Nootkatone controls the NAG-1 expression at the transcriptional level. a Nootkatone increases NAG-1 promoter activity. HCT-116 cells were transfected with pNAG-1 − 1086/+ 41 luciferase and pRL-null plasmid. The cells were treated with EtOH or various concentrations of nootkatone for 24 h, and luciferase activity was measured. The y-axis refers to the ratio of firefly luciferase over renillar luciferase activity. The EtOH-treated cells were set as 1.0. Statistical significance was displayed as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. b Three deletion NAG-1 promoter constructs were co-transfected with pRL-null vector into HCT-116 cells. The cells were treated with EtOH or 100 μM of nootkatone for 24 h, and luciferase activity was measured. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells versus EtOH-treated cells. Statistical significance was displayed as **p < 0.01 and ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. c HCT-116 cells were co-transfected with wild type pNAG-1 − 133/+ 41 in the presence of empty or EGR-1 expression vector. Cells were subsequently treated with 100 μM nootkatone for 24 h. The results are presented as means ± S.D. of three independent transfections. d Western blot of EGR-1 protein in the presence of nootkatone. β-actin was used as loading control. e Luciferase activity of EGR-1 promoter-luciferase construct (pEGR-1260-LUC). The cells were treated with EtOH or
nootkatone for 24 h prior to measurement of luciferase activity. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells compared to EtOH-treated cells. Statistical significance represented as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. n.s. represents not significant. The data represent mean ± SD from four independent experiments
Yoo et al. BMC Cancer (2020) 20:881 Page 10 of 12 funding agency did not have any influence in the design of the study and
collection, analysis, and interpretation of data and in writing the manuscript.		ko_KR
dc.language.isoenko_KR
dc.publisherBMCko_KR
dc.subjectNootkatone-
dc.subjectNAG-1-
dc.subjectCyclin D1-
dc.subjectA. oxyphylla-
dc.titleAnti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cellsko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor유은수-
dc.contributor.AlternativeAuthor이재학-
dc.contributor.AlternativeAuthor류준선-
dc.contributor.AlternativeAuthor김종태-
dc.contributor.AlternativeAuthor박을용-
dc.contributor.AlternativeAuthor백성준-
dc.identifier.doidoi.org/10.1186/s12885-020-07379-y-
dc.citation.journaltitleBMC Cancerko_KR
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2020-09-20T03:32:09Z-
dc.citation.number1ko_KR
dc.citation.startpage881ko_KR
dc.citation.volume20ko_KR
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