Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
Oncol Rep. 2012 Oct;28(4):1512-8. doi: 10.3892/or.2012.1947. Epub 2012 Aug 3.
Fucoxanthin (FX) is a natural carotenoid with reported antitumorigenic activity. This study explored the effects of FX and its deacetylated product, fucoxanthinol (FXOH), on B-cell malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma and Epstein-Barr virus-immortalized B cells. Both FX and FXOH reduced the viability of these malignant B cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during G1 phase and caspase-dependent apoptosis. FXOH was approximately twice more potent than FX in these activities. In contrast, normal peripheral blood mononuclear cells were resistant to FX and FXOH. Strong and constitutive activation of nuclear factor-κB (NF-κB) is a common characteristic of many B-cell malignancies, and FXOH suppressed constitutive NF-κB activity. NF-κB inhibition was accompanied by downregulation of NF-κB-dependent anti-apoptotic and cell cycle regulator gene products, including Bcl-2, cIAP-2, XIAP, cyclin D1 and cyclin D2. The results indicated that FX and FXOH are potentially useful therapeutic agents in B-cell malignancies characterized by aberrant regulation of NF-κB.
岩藻黄质(FX)是一种天然类胡萝卜素,具有抗肿瘤活性。本研究探讨了 FX 及其去乙酰化产物岩藻黄醇(FXOH)对 B 细胞恶性肿瘤的作用,包括 Burkitt 淋巴瘤、霍奇金淋巴瘤和 Epstein-Barr 病毒永生化 B 细胞。FX 和 FXOH 均能以剂量依赖的方式降低这些恶性 B 细胞的活力,同时诱导 G1 期细胞周期停滞和 caspase 依赖性细胞凋亡。在这些活性中,FXOH 的作用约为 FX 的两倍。相比之下,正常外周血单个核细胞对 FX 和 FXOH 具有抗性。核因子-κB(NF-κB)的强烈和组成性激活是许多 B 细胞恶性肿瘤的共同特征,而 FXOH 抑制了 NF-κB 的组成性活性。NF-κB 抑制伴随着 NF-κB 依赖性抗凋亡和细胞周期调节剂基因产物的下调,包括 Bcl-2、cIAP-2、XIAP、cyclin D1 和 cyclin D2。结果表明,FX 和 FXOH 可能是 NF-κB 异常调节的 B 细胞恶性肿瘤的潜在有用治疗剂。