Preprint Article Version 1 This version is not peer-reviewed

Inhibition of Wnt3a/FOXM1/β-Catenin Axis and Activation of GSK 3β and Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast Cancers

Version 1 : Received: 23 August 2018 / Approved: 24 August 2018 / Online: 24 August 2018 (10:58:08 CEST)

A peer-reviewed article of this Preprint also exists.

Hwang, S.M.; Lee, H.-J.; Jung, J.H.; Sim, D.Y.; Hwang, J.; Park, J.E.; Shim, B.S.; Kim, S.-H. 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, 19, 2681. Hwang, S.M.; Lee, H.-J.; Jung, J.H.; Sim, D.Y.; Hwang, J.; Park, J.E.; Shim, B.S.; Kim, S.-H. 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, 19, 2681.

Journal reference: Int. J. Mol. Sci. 2018, 19, 2681
DOI: 10.3390/ijms19092681

Abstract

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so 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-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), 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 (GSK 3β) 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 caspase and GSK3β

Subject Areas

Breast cancer; Moracin D; Apoptosis; FOXM1; β-catenin;GSK 3β

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