Natural compound So-2 suppresses triple-negative breast cancer through inducing ferroptosis via downregulating transcription factor E2F7

Na Liu; Zhang Jing; Duan Wen-Qi; Luo Ting-Ting; Wu Cong; Han Li-Na; Yang Feng-Ying; Yue Hong-Wei; Ge Di

doi:10.1016/j.abb.2023.109694

Natural compound So-2 suppresses triple-negative breast cancer through inducing ferroptosis via downregulating transcription factor E2F7

Arch Biochem Biophys. 2023 Aug:744:109694. doi: 10.1016/j.abb.2023.109694. Epub 2023 Jul 20.

Authors

Na Liu¹, Zhang Jing¹, Duan Wen-Qi¹, Luo Ting-Ting¹, Wu Cong¹, Han Li-Na¹, Yang Feng-Ying¹, Yue Hong-Wei², Ge Di³

Affiliations

¹ School of Biological Science and Technology, University of Jinan, Jinan, 250024, China.
² Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China. Electronic address: talatala@126.com.
³ School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: bio_ged@ujn.edu.cn.

PMID: 37481196
DOI: 10.1016/j.abb.2023.109694

Abstract

Triple-negative breast cancer (TNBC), accounting for about 15∼18% of all breast cancers, is notorious for its poor prognosis, high rate of relapse and short overall survival. Because of lacking effective therapeutic targets or drugs, treatment of TNBC in clinical encounters great obstacle. Siegesbeckiaorientalis L. have been used as a traditional Chinese medicine "Xi-Xian-Cao" for centuries with multiple medicinal benefits including cancerous treatment. We have reported the isolation of twenty-seven germacranolides including So-2 from the aerial parts of S. orientalis with potent cytotoxicity against breast cancer cells. The studyaims to verified the anti-TNBC function of the natural compound So-2 both in vitro and vivo and uncover the underlying mechanism. The results showed that So-2 caused cell cycle arrest and suppress TNBC cell proliferation and migration. Also, So-2 was first identified to be a bona fide ferroptosis inducer in TNBC cells. So-2 effectively suppressed tumor growth of TNBC by using an orthotopic transplantation tumor model. We also characterized the oncogenic role of the transcription factor E2F7 in TNBC. E2F7 was demonstrated to be involved in the ferroptosis-inducing and tumor suppression effect of So-2. Altogether, So-2 exhibits inhibitory effect on TNBC both in vitro and vivo by inducing TNBC ferroptosis via downregulating the expression of E2F7. These findings provide valuable insight into the pathogenesis of TNBC. The natural compound So-2, isolated from Chinese traditional medicine, might be a prospective drug candidate in TNBC therapy.

Keywords: Cell migration; E2F7; Ferroptosis; Natural compound; Sesquiterpenoids; TNBC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation
E2F7 Transcription Factor
Ferroptosis*
Humans
Transcription Factors
Triple Negative Breast Neoplasms* / drug therapy

Substances

E2F7 protein, human
E2F7 Transcription Factor
Transcription Factors