2. Academic Validation
  3. 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

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

  • Int J Mol Sci. 2018 Sep 10;19(9):2681. doi: 10.3390/ijms19092681.
Sung Min Hwang 1,  Hyo-Jung Lee 2,  Ji Hoon Jung 3,  Deok Yong Sim 4,  Jisung Hwang 5,  Ji Eon Park 6,  Bum Sang Shim 7,  Sung-Hoon Kim 8
Affiliations

Affiliations

  • 1 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. pneuma1@hanmail.net.
  • 2 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. hyonice77@naver.com.
  • 3 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. johnsperfume@gmail.com.
  • 4 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. simdy0821@naver.com.
  • 5 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. hjsung0103@naver.com.
  • 6 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. wdnk77@naver.com.
  • 7 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. eshimbs@khu.ac.kr.
  • 8 College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. sungkim7@khu.ac.kr.
PMID: 30201862 DOI: 10.3390/ijms19092681
Abstract

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.

Keywords

FOXM1; GSK3β; Moracin D; apoptosis; breast cancer; β-catenin.

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