Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling

Chen, Yueqiang; Song, Haiyan; Zhou, Zhong-Yan; Ma, Jiao; Luo, Zhanyang; Zhou, Ying; Wang, Jianyi; Liu, Sheng; Han, Xin

doi:10.1038/s41401-021-00757-7

Cited by 11 publications

(5 citation statements)

References 55 publications

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“…Previous studies reported the potential anti‐RA effect of OS 25,26 . In addition, OS has an inhibitory impact on cell proliferation, migration, and invasion 27,28 . In the present investigation, we found that OS not only inhibited RA‐FLS proliferation, migration, and invasion but also showed an additive effect with MTX.…”

Section: Discussionsupporting

confidence: 70%

“…25,26 In addition, OS has an inhibitory impact on cell proliferation, migration, and invasion. 27,28 In the present investigation, we found that OS not only inhibited RA-FLS proliferation, migration, and invasion but also showed an additive effect with MTX. In the subsequent study, we showed that OS reduced NF-κB signaling activity to exert its anti-RA effect, which was consistent with another report indicating the role of NF-κB signaling in regulating RA-FLS proliferation, migration, and invasion.…”

Section: Discussionsupporting

confidence: 58%

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Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Lin

Chen

Tao

et al. 2023

MedComm

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Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and RA interstitial lung disease (ILD) is a severe complication of RA. This investigation aims to determine the effect and underlying mechanism of osthole (OS), which could be extracted from Cnidium , Angelica , and Citrus plants and evaluate the role of transglutaminase 2 (TGM2) in RA and RA‐ILD. In this work, OS downregulated TGM2 to exert its additive effect with methotrexate and suppress the proliferation, migration, and invasion of RA‐fibroblast‐like synoviocytes (FLS) by attenuating NF‐κB signaling, resulting in the suppression of RA progression. Interestingly, WTAP‐mediated N6‐methyladenosine modification of TGM2 and Myc‐mediated WTAP transcription cooperatively contributed to the formation of a TGM2/Myc/WTAP‐positive feedback loop through upregulating NF‐κB signaling. Moreover, OS could downregulate the activation of the TGM2/Myc/WTAP‐positive feedback circuit. Furthermore, OS restrained the proliferation and polarization of M2 macrophages to inhibit the aggregation of lung interstitial CD11b + macrophages, and the effectiveness and non‐toxicity of OS in suppressing RA and RA‐ILD progression were verified in vivo. Finally, bioinformatics analyses validated the importance and the clinical significance of the OS‐regulated molecular network. Taken together, our work emphasized OS as an effective drug candidate and TGM2 as a promising target for RA and RA‐ILD treatment.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 58%

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Lin

Chen

Tao

et al. 2023

MedComm

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“…Its protein product X-box binding protein 1 (XBP1) regulates the expression of fibronectin-1 (FN1) at the mRNA level, which transmits signals to Src/FAK/Rac1 via integrins [ 110 ]. By downregulating the integrin-triggered FAK/Src signaling pathway, integrin can inhibit EMT and attenuate the invasion and migration of breast cancer cells [ 111 ]. The signals transmitted from integrins to FAK can also activate Rac1 through PI3K/Akt, inducing actin cytoskeleton rearrangement and accelerating cell migration [ 112 ].…”

Section: Molecular Mechanisms Of Cell Migration Regulated By Rac1mentioning

confidence: 99%

Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy

Luo

et al. 2023

Molecules

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Cell migration is crucial for physiological and pathological processes such as morphogenesis, wound repair, immune response and cancer invasion/metastasis. There are many factors affecting cell migration, and the regulatory mechanisms are complex. Rac1 is a GTP-binding protein with small molecular weight belonging to the Rac subfamily of the Rho GTPase family. As a key molecule in regulating cell migration, Rac1 participates in signal transduction from the external cell to the actin cytoskeleton and promotes the establishment of cell polarity which plays an important role in cancer cell invasion/metastasis. In this review, we firstly introduce the molecular structure and activity regulation of Rac1, and then summarize the role of Rac1 in cancer invasion/metastasis and other physiological processes. We also discuss the regulatory mechanisms of Rac1 in cell migration and highlight it as a potential target in cancer therapy. Finally, the current state as well as the future challenges in this area are considered. Understanding the role and the regulatory mechanism of Rac1 in cell migration can provide fundamental insights into Rac1-related cancer progression and further help us to develop novel intervention strategies for cancer therapy in clinic.

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“…Osthole with IC 50 values of 24.2, 6.8, and 123.9 μg/ml (48 h) against MDA-MB-231, MDA-MB-231BO, and MCF-7 cells. Besides, osthole displayed a lower cytotoxicity against normal MCF-10A cells with an IC 50 value of 8944.0 μg/ml ( Chen et al, 2021 ). A recent study demonstrated that low G protein gamma subunit 7 expression in breast cancer tissues was associated with shorter overall and relapse-free survival and that osthole targeted G protein gamma subunit 7 to inhibit cell proliferation and promote apoptosis in breast cancer cell lines (MDA-MB-231, MCF-7; Mei et al, 2021 ).…”

Section: Anticancer Mechanism Of Osthole In Various Organ Systemsmentioning

confidence: 99%

Osthole: An up-to-date review of its anticancer potential and mechanisms of action

et al. 2022

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With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.

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Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling

Cited by 11 publications

References 55 publications

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy

Osthole: An up-to-date review of its anticancer potential and mechanisms of action

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