Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells

α-Cubebenoate derived from <i>Schisandra chinensis</i> has been reported to possess anti-allergic, anti-obesity, and anti-inflammatory effects and to exhibit anti-septic activity, but its anti-cancer effects have not been investigated. To examine the anti-cancer activity of α-cubebenoate...

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Main Authors: Jeong Eun Gong, Ji Eun Kim, Su Jin Lee, Yun Ju Choi, You Jeong Jin, Young Whan Choi, Sun Il Choi, Dae Youn Hwang
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/3/737
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author Jeong Eun Gong
Ji Eun Kim
Su Jin Lee
Yun Ju Choi
You Jeong Jin
Young Whan Choi
Sun Il Choi
Dae Youn Hwang
author_facet Jeong Eun Gong
Ji Eun Kim
Su Jin Lee
Yun Ju Choi
You Jeong Jin
Young Whan Choi
Sun Il Choi
Dae Youn Hwang
author_sort Jeong Eun Gong
collection DOAJ
description α-Cubebenoate derived from <i>Schisandra chinensis</i> has been reported to possess anti-allergic, anti-obesity, and anti-inflammatory effects and to exhibit anti-septic activity, but its anti-cancer effects have not been investigated. To examine the anti-cancer activity of α-cubebenoate, we investigated its effects on the proliferation, apoptosis, and metastasis of CT26 cells. The viabilities of CT26 cells (a murine colorectal carcinoma cell line) and HCT116 cells (a human colon cancer cell line) were remarkably and dose-dependently diminished by α-cubebenoate, whereas the viability of CCD-18Co cells (a normal human fibroblast cell line) were unaffected. Furthermore, α-cubebenoate treatment increased the number of apoptotic CT26 cells as compared with Vehicle-treated cells and increased Bax, Bcl-2, Cas-3, and Cleaved Cas-3 protein levels by activating the MAP kinase signaling pathway. α-Cubebenoate also suppressed CT26 migration by regulating the PI3K/AKT signaling pathway. Furthermore, similar reductions were observed in the expression levels of some migration-related proteins including VEGFA, MMP2, and MMP9. Furthermore, reduced VEGFA expression was found to be accompanied by the phosphorylations of FAK and MLC in the downstream signaling pathway of adhesion protein. The results of the present study provide novel evidence that α-cubebenoate can stimulate apoptosis and inhibit metastasis by regulating the MAPK, PI3K/AKT, and FAK/MLC signaling pathways.
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spelling doaj.art-631ba68e48714b8ab760feef079e5dad2023-11-23T17:11:39ZengMDPI AGMolecules1420-30492022-01-0127373710.3390/molecules27030737Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer CellsJeong Eun Gong0Ji Eun Kim1Su Jin Lee2Yun Ju Choi3You Jeong Jin4Young Whan Choi5Sun Il Choi6Dae Youn Hwang7Laboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, KoreaLaboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, KoreaLaboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, KoreaLaboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, KoreaLaboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, KoreaDepartment of Horticultural Bioscience, Pusan National University, Miryang 50463, KoreaSchool of Pharmacy, Henan University, Kaifeng 475004, ChinaLaboratory Animal Resources Center, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources & Life Science, Pusan National University, Miryang 50463, Koreaα-Cubebenoate derived from <i>Schisandra chinensis</i> has been reported to possess anti-allergic, anti-obesity, and anti-inflammatory effects and to exhibit anti-septic activity, but its anti-cancer effects have not been investigated. To examine the anti-cancer activity of α-cubebenoate, we investigated its effects on the proliferation, apoptosis, and metastasis of CT26 cells. The viabilities of CT26 cells (a murine colorectal carcinoma cell line) and HCT116 cells (a human colon cancer cell line) were remarkably and dose-dependently diminished by α-cubebenoate, whereas the viability of CCD-18Co cells (a normal human fibroblast cell line) were unaffected. Furthermore, α-cubebenoate treatment increased the number of apoptotic CT26 cells as compared with Vehicle-treated cells and increased Bax, Bcl-2, Cas-3, and Cleaved Cas-3 protein levels by activating the MAP kinase signaling pathway. α-Cubebenoate also suppressed CT26 migration by regulating the PI3K/AKT signaling pathway. Furthermore, similar reductions were observed in the expression levels of some migration-related proteins including VEGFA, MMP2, and MMP9. Furthermore, reduced VEGFA expression was found to be accompanied by the phosphorylations of FAK and MLC in the downstream signaling pathway of adhesion protein. The results of the present study provide novel evidence that α-cubebenoate can stimulate apoptosis and inhibit metastasis by regulating the MAPK, PI3K/AKT, and FAK/MLC signaling pathways.https://www.mdpi.com/1420-3049/27/3/737α-cubebenoateCT26 colon cancerapoptosismigrationFAK/MLC
spellingShingle Jeong Eun Gong
Ji Eun Kim
Su Jin Lee
Yun Ju Choi
You Jeong Jin
Young Whan Choi
Sun Il Choi
Dae Youn Hwang
Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
Molecules
α-cubebenoate
CT26 colon cancer
apoptosis
migration
FAK/MLC
title Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
title_full Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
title_fullStr Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
title_full_unstemmed Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
title_short Anti-Cancer Effects of α-Cubebenoate Derived from <i>Schisandra chinensis</i> in CT26 Colon Cancer Cells
title_sort anti cancer effects of α cubebenoate derived from i schisandra chinensis i in ct26 colon cancer cells
topic α-cubebenoate
CT26 colon cancer
apoptosis
migration
FAK/MLC
url https://www.mdpi.com/1420-3049/27/3/737
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