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海洋过氧倍半萜通过调节 HCT116 结肠癌细胞的 Nrf2-ARE 信号诱导细胞凋亡。

Marine Peroxy Sesquiterpenoids Induce Apoptosis by Modulation of Nrf2-ARE Signaling in HCT116 Colon Cancer Cells.

机构信息

Department Bioresource Technology, Okinawa National College of Technology, 905 Henoko, Nago-city Okinawa Prefecture 905-2192, Japan.

Department of Chemistry, Biology and Marine Science, University of the Ryukyus, 1 Senbaru, Nishihara-cho, Okinawa 903-2013, Japan.

出版信息

Mar Drugs. 2018 Sep 23;16(10):347. doi: 10.3390/md16100347.

Abstract

Our current study demonstrated that the marine peroxy sesquiterpenoids isolated from the Okinawan soft coral sp. have an antitumor activity in human colon cancer cell (HCT) 116 colon cancer cells with their induction of apoptosis due to H₂O₂ production derived from the compounds. This study clarified that peroxy sesquiterpenoids ( and ) inhibited anti-apoptosis proteins, such as B-cell lymphoma-extra large (Bcl-xL) and phosphoAkt (pAkt). In addition, the heme oxygenase-1 (HO-1), nuclear factor-erythroid-2-related factor (Nrf2), and phosphoNrf2 (pNrf2) proteins related to the cell survival regulation signal of Nrf2-ARE (antioxidant response element) were also suppressed in the presence of these compounds. While the cells treated with the compounds and trolox as an antioxidant expressed the inhibited proteins, such as HO-1, Nrf2, and Bcl-xL, it was suggested that the H₂O₂ involving free radical reactions derived from the molecule would be a trigger of apoptosis with the modulation of Nrf2-ARE signaling in the cells.

摘要

我们的研究表明,从冲绳软珊瑚中分离得到的海洋过氧倍半萜具有抗肿瘤活性,能够诱导人结肠癌细胞(HCT116)凋亡,这是由于化合物产生的 H₂O₂所致。本研究表明,过氧倍半萜(和)抑制抗凋亡蛋白,如 B 细胞淋巴瘤-extra large(Bcl-xL)和磷酸化 Akt(pAkt)。此外,血红素加氧酶-1(HO-1)、核因子-红细胞 2 相关因子(Nrf2)和磷酸化 Nrf2(pNrf2)与 Nrf2-ARE(抗氧化反应元件)细胞存活调节信号相关的蛋白也被这些化合物抑制。当用化合物和 Trolox(一种抗氧化剂)处理细胞时,表达了抑制蛋白,如 HO-1、Nrf2 和 Bcl-xL,这表明源自该分子的涉及自由基反应的 H₂O₂可能是细胞中 Nrf2-ARE 信号转导调节的凋亡触发因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6c/6213732/a9bd6d6ed498/marinedrugs-16-00347-g001.jpg

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