Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Russelioside A, a Pregnane Glycoside from Caralluma tuberculate, Inhibits Cell-Intrinsic NF-κB Activity and Metastatic Ability of Breast Cancer Cells
Rahma Tharwat SabraAmira A. AbdellatefEssam Abdel-SattarMoustafa FathyMeselhy R. MeselhyYoshihiro Hayakawa
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2022 年 45 巻 10 号 p. 1564-1571

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Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a potential target for inflammatory-breast cancer treatment as it participates in its pathogenesis, such as tumor initiation, progression, survival, metastasis, and recurrence. In this study, we aimed to discover a novel anti-cancer treatment from natural products by targeting NF-κB activity. Using the 4T1-NFκB-luciferase reporter cell line, we tested three pregnane glycosides extracted from the herb Caralluma tuberculata and discovered that Russelioside A markedly suppressed NF-κB activity in breast cancer. Russelioside A inhibited NF-κB (p65) transcriptional activity and its phosphorylation. Following NF-κB inhibition, Russelioside A exerted anti-proliferative and anti-metastatic effects in breast cancer cells in vitro. Moreover, it inhibited the NF-κB constitutive expression of downstream pathways, such as VEGF-b, MMP-9, and IL-6 in 4T1 cells. In addition, it reduced the metastatic capacity in a 4T1 breast cancer model in vivo. Collectively, our conclusions reveal that Russelioside A is an attractive natural compound for treating triple-negative breast cancer growth and metastasis through regulating NF-κB activation.

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