The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol exhibits anticancer activity by regulating multiple signaling pathways in human glioblastoma cells: Blocking EGF signaling.

Masayoshi Yamaguchi, Kenji Yoshiike, Katsuya Kuroki, Hideaki Watanabe, Mitsugu Watanabe
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Abstract

Glioblastoma is the most common adult malignant brain tumor. This tumor is aggressive and the most lethal. Trials to improve the outcome of patients with this tumor remain critical. There are no effective therapies for malignant glioma. Glioblastoma is characterized by ligand-independent overexpression of epidermal growth factor (EGF) receptors. EGF receptor signaling can promote tumorigenesis by increasing cell proliferation and tissue invasion and by inhibiting apoptosis of cancer cells. The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has been shown to block oxidative stress by scavenging free radicals in various cell types. This study investigates the effects of DHMBA on human glioblastoma cells in vitro. Glioblastoma cells were cultured in DMEM-low glucose containing 10% fetal bovine serum (FBS) in the presence of DHMBA (0.1-250 μM). Culturing with DHMBA significantly suppressed cell proliferation in the presence of FBS or EGF. Mechanistically, DHMBA treatment significantly decreased the levels of PI3-kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR, which are promoters of cell growth, and increased the levels of tumor suppressors p53, p21, and Rb, leading to the reduction of cancer cell growth. DHMBA treatment significantly stimulated the death of glioblastoma cells by increasing the levels of caspase-3 and cleaved caspase-3. In addition, culture with DHMBA significantly inhibited metastatic activity, including adhesion and migration of cancer cells. Thus, DHMBA may have inhibitory effects on the activity of human glioblastoma cells in vitro. This study may provide a new strategy for the treatment of glioblastoma tumors.

新型海洋因子 3,5-二羟基-4-甲氧基苄醇通过调节人类胶质母细胞瘤细胞的多种信号通路而表现出抗癌活性:阻断 EGF 信号传导。
胶质母细胞瘤是最常见的成人恶性脑肿瘤。这种肿瘤具有侵袭性,也是最致命的肿瘤。改善该肿瘤患者预后的试验仍然至关重要。恶性胶质瘤目前尚无有效的治疗方法。胶质母细胞瘤的特点是不依赖配体的表皮生长因子(EGF)受体过度表达。表皮生长因子受体信号可通过增加细胞增殖和组织侵袭以及抑制癌细胞凋亡来促进肿瘤发生。海洋因子 3,5-二羟基-4-甲氧基苄醇(DHMBA)已被证明可通过清除各种细胞中的自由基来阻断氧化应激。本研究调查了 DHMBA 对体外人类胶质母细胞瘤细胞的影响。胶质母细胞瘤细胞在含有 10%胎牛血清(FBS)的 DMEM 低葡萄糖培养液中培养,DHMBA(0.1-250 μM)存在。在有 FBS 或 EGF 存在的情况下,用 DHMBA 培养可明显抑制细胞增殖。从机理上讲,DHMBA 能明显降低促进细胞生长的 PI3 激酶 100α、Akt、MAPK、phosphor-MAPK 和 mTOR 的水平,提高肿瘤抑制因子 p53、p21 和 Rb 的水平,从而降低癌细胞的生长。DHMBA 通过提高 caspase-3 和裂解 caspase-3 的水平,明显刺激胶质母细胞瘤细胞的死亡。此外,用 DHMBA 培养可明显抑制癌细胞的转移活性,包括粘附和迁移。因此,DHMBA 可能对体外人类胶质母细胞瘤细胞的活性有抑制作用。这项研究可为治疗胶质母细胞瘤肿瘤提供一种新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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