Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers
Although Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D has not been unveiled thus far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Mo...
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doaj-1c176321d9fa453ab8f1d45a23cd51f82020-11-24T22:04:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-09-01199268110.3390/ijms19092681ijms19092681Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast CancersSung Min Hwang0Hyo-Jung Lee1Ji Hoon Jung2Deok Yong Sim3Jisung Hwang4Ji Eon Park5Bum Sang Shim6Sung-Hoon Kim7College of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaAlthough Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D has not been unveiled thus far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB-231 and MCF-7 cells. Furthermore, Moracin D increased sub G1 population; cleaved poly (Adenosine diphosphate (ADP-ribose)) polymerase (PARP); activated cysteine aspartyl-specific protease 3 (caspase 3); and attenuated the expression of c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2), and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3, and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspases and GSK3β.http://www.mdpi.com/1422-0067/19/9/2681breast cancerMoracin DapoptosisFOXM1β-cateninGSK3β |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sung Min Hwang Hyo-Jung Lee Ji Hoon Jung Deok Yong Sim Jisung Hwang Ji Eon Park Bum Sang Shim Sung-Hoon Kim |
spellingShingle |
Sung Min Hwang Hyo-Jung Lee Ji Hoon Jung Deok Yong Sim Jisung Hwang Ji Eon Park Bum Sang Shim Sung-Hoon Kim Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers International Journal of Molecular Sciences breast cancer Moracin D apoptosis FOXM1 β-catenin GSK3β |
author_facet |
Sung Min Hwang Hyo-Jung Lee Ji Hoon Jung Deok Yong Sim Jisung Hwang Ji Eon Park Bum Sang Shim Sung-Hoon Kim |
author_sort |
Sung Min Hwang |
title |
Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers |
title_short |
Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers |
title_full |
Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers |
title_fullStr |
Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers |
title_full_unstemmed |
Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers |
title_sort |
inhibition of wnt3a/foxm1/β-catenin axis and activation of gsk3β and caspases are critically involved in apoptotic effect of moracin d in breast cancers |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-09-01 |
description |
Although Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D has not been unveiled thus far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB-231 and MCF-7 cells. Furthermore, Moracin D increased sub G1 population; cleaved poly (Adenosine diphosphate (ADP-ribose)) polymerase (PARP); activated cysteine aspartyl-specific protease 3 (caspase 3); and attenuated the expression of c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2), and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3, and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspases and GSK3β. |
topic |
breast cancer Moracin D apoptosis FOXM1 β-catenin GSK3β |
url |
http://www.mdpi.com/1422-0067/19/9/2681 |
work_keys_str_mv |
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