Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.
Natural Medicine Research Center, Bio-Therapeutics Research Institute, Korea Research Institute of Bioscience & Biotechnology, Chungbuk, Republic of Korea.
Environ Toxicol. 2018 Nov;33(11):1143-1152. doi: 10.1002/tox.22620. Epub 2018 Aug 22.
7-Methoxy-luteolin-8-C-β-6-deoxy-xylo-pyranos-3-uloside (mLU8C-PU) is a glycosylflavone of luteolin isolated from Arthraxon hispidus (Thunb.). Luteolin is known to exert anti-migratory and anti-invasive effects on tumor cells. However, there are no reports on the effects of mLU8C-PU on tumor invasiveness and associated signaling pathways. In this study, we demonstrated the anti-migratory and anti-invasive effects of mLU8C-PU in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. We also investigated the effect of mLU8C-PU on invasion- related signal transducers, including protein kinase Cα (PKCα), c-Jun N terminal kinase (JNK), activator protein-1 (AP-1), and nuclear factor-kappa B (NF-ĸB). TPA-induced membrane translocation of PKCα, phosphorylation of JNK, and the nuclear translocations of AP-1 and NF-κB were downregulated by mLU8C-PU in MCF-7 cells. In addition, mLU8C-PU also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. These results indicate that mLU8C-PU inhibits migratory and invasive responses in MCF-7 breast cancer cells by suppressing MMP-9 and IL-8 expression through mitigating TPA-induced PKCα, JNK activation, and the nuclear translocation of AP-1 and NF-κB. These results suggest that mLU8C-PU may be used as an anti-metastatic agent.
7-甲氧基木犀草素-8-C-β-6-去氧吡喃木糖-3-基芦丁糖苷(mLU8C-PU)是从鬼箭羽(Thunb.)中分离得到的木犀草素的糖基黄酮。木犀草素已被证明对肿瘤细胞具有抗迁移和抗侵袭作用。然而,目前尚无关于 mLU8C-PU 对肿瘤侵袭性和相关信号通路影响的报道。在本研究中,我们证明了 mLU8C-PU 在 12-O-十四烷酰佛波醇-13-乙酸酯(TPA)处理的 MCF-7 乳腺癌细胞中的抗迁移和抗侵袭作用。我们还研究了 mLU8C-PU 对侵袭相关信号转导物的影响,包括蛋白激酶 Cα(PKCα)、c-Jun N 末端激酶(JNK)、激活蛋白-1(AP-1)和核因子-κB(NF-κB)。mLU8C-PU 下调 TPA 诱导的 MCF-7 细胞中 PKCα 的膜易位、JNK 的磷酸化以及 AP-1 和 NF-κB 的核易位。此外,mLU8C-PU 还抑制基质金属蛋白酶-9(MMP-9)和白细胞介素-8(IL-8)的表达。这些结果表明,mLU8C-PU 通过抑制 MMP-9 和 IL-8 的表达,抑制 MCF-7 乳腺癌细胞的迁移和侵袭反应,其机制可能是通过抑制 TPA 诱导的 PKCα、JNK 激活以及 AP-1 和 NF-κB 的核易位。这些结果表明,mLU8C-PU 可能可用作抗转移剂。