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Maclurin 通过氧化活性和 PARP、p38 和 ERK 信号通路的调节发挥对人骨肉瘤细胞的抗癌作用。

Maclurin exerts anti-cancer effects in human osteosarcoma cells via prooxidative activity and modulations of PARP, p38, and ERK signaling.

机构信息

Department of Life Science, Gachon University, Seongnam, South Korea.

出版信息

IUBMB Life. 2021 Aug;73(8):1060-1072. doi: 10.1002/iub.2506. Epub 2021 May 28.

DOI:10.1002/iub.2506
PMID:34003554
Abstract

Maclurin [(3,4-dihydroxyphenyl)-(2,4,6-trihydroxyphenyl) methanone] is a natural compound that can be extracted from white mulberry(Morus alba) and purple mangosteen(Garcinia mangostana). Maclurin is known for its dual-sided effect on reactive oxygen species (ROS). Osteosarcoma is a primary malignant tumor of the bone and is one of the most aggressive cancers. It is common especially in children and young adults and can progress into highly metastatic cancer. In this study, we investigated the anti-cancer effects of maclurin on U2OS human osteosarcoma cells. The results indicated that maclurin exerts prooxidative effects and induces apoptosis via capase-3-independent PARP regulation in U2OS human osteosarcoma cells. Maclurin also inhibits the migration of U2OS human osteosarcoma cells. Maclurin modulates two of the three major mitogen-activated protein kinases that are closely linked with cancer metastasis; that is, it activates p38 and inactivates Extracellular signal-regulated kinase. The apoptosis-inducing effects of maclurin on U2OS osteosarcoma cells were diminished by additional treatment with antioxidant N-acetyl cysteine (NAC), but the migration-inhibiting effect was not affected by NAC treatment. This further suggested the only apoptosis-inducing effect of maclurin may be strongly related to its prooxidative activity. Taken together, these results suggested that maclurin may be a strong candidate molecule as an anti-osteosarcoma agent.

摘要

马栗灵[(3,4-二羟基苯基)-(2,4,6-三羟基苯基)甲酮]是一种天然化合物,可从白桑(Morus alba)和山竹(Garcinia mangostana)中提取。马栗灵因其对活性氧(ROS)的双面作用而闻名。骨肉瘤是一种原发性骨恶性肿瘤,是最具侵袭性的癌症之一。它在儿童和年轻人中很常见,可进展为高度转移性癌症。在这项研究中,我们研究了马栗灵对 U2OS 人骨肉瘤细胞的抗癌作用。结果表明,马栗灵在 U2OS 人骨肉瘤细胞中发挥促氧化作用,并通过 caspase-3 非依赖性 PARP 调节诱导细胞凋亡。马栗灵还抑制 U2OS 人骨肉瘤细胞的迁移。马栗灵调节与癌症转移密切相关的三种主要丝裂原活化蛋白激酶中的两种;即,它激活 p38 并使细胞外信号调节激酶失活。抗氧化剂 N-乙酰半胱氨酸(NAC)的额外处理可减弱马栗灵对 U2OS 骨肉瘤细胞的凋亡诱导作用,但 NAC 处理并不影响其抑制迁移的作用。这进一步表明马栗灵的仅诱导凋亡作用可能与其促氧化活性密切相关。综上所述,这些结果表明马栗灵可能是一种强大的候选分子,可作为抗骨肉瘤药物。

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