Delayed growth of glioma by Scutellaria flavonoids involve inhibition of Akt, GSK-3 and NF-κB signaling.
Delayed growth of glioma by Scutellaria flavonoids involve inhibition of Akt, GSK-3 and NF-κB signaling.
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DOI：
10.1007/s11060-010-0221-x
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发表时间：
2011-01
影响因子：
3.9
通讯作者：
Yadav AK
中科院分区：
文献类型：
--
作者：
Parajuli P;Joshee N;Chinni SR;Rimando AM;Mittal S;Sethi S;Yadav AK
紫茎泽兰属植物构成东方以及传统美国医学的常见成分之一，用于治疗各种人类疾病，包括癌症。在这项研究中，我们研究了在体内抗胶质瘤活性的一个叶提取物的紫藤ocmulgee（SocL），同时也探索其潜在的分子作用机制。在颅内和皮下肿瘤模型中，口服SocL提取物可延缓F344大鼠F98胶质瘤的生长。免疫组化显示，用紫藤处理后，皮下肿瘤中Akt、GSK-3α/β和NF-κB磷酸化受到抑制。Western印迹分析表明，SocL提取物和汉黄芩素对F98细胞Akt、GSK-3α/β和NF-κB的抑制作用呈剂量和时间依赖性。PI 3 K和NF-κB的药理学抑制剂也显著抑制F98胶质瘤细胞的体外增殖，表明这些信号分子在恶性胶质瘤生长中的关键作用。然而，转染F98细胞与组成型活性突变体的AKT（AKT/CA），并没有显着逆转紫藤介导的增殖抑制，表明紫藤黄酮类化合物直接抑制Akt激酶活性或作用于Akt的下游。体外Akt激酶活性测定结果表明，SocL提取物或汉黄芩素确实能与Akt结合并抑制其激酶活性。这项研究提供了第一个在体内的证据和机制的支持，抗胶质瘤活性的紫藤黄酮类化合物，并在辅助治疗恶性肿瘤，包括胶质瘤的潜在用途的影响。
Plants of the genus Scutellaria constitute one of the common components of Eastern as well as traditional American medicine against various human diseases, including cancer. In this study, we examined the in vivo anti-glioma activity of a leaf extract of Scutellaria ocmulgee (SocL) while also exploring their potential molecular mechanisms of action. Oral administration of SocL extract delayed the growth of F98 glioma in F344 rats, both in intracranial and subcutaneous tumor models. Immunohistochemistry revealed inhibition of Akt, GSK-3α/β and NF-κB phosphorylation in the subcutaneous tumors following treatment with Scutellaria. The SocL extract as well as the constituent flavonoid wogonin also showed dose- and time-dependent inhibition of Akt, GSK-3α/β and NF-κB in F98 cell cultures in vitro, as determined by western blot analysis. Pharmacologic inhibitors of PI3K and NF-κB also significantly inhibited the in vitro proliferation of F98 glioma cells, indicating the key role of these signaling molecules in the growth of malignant gliomas. Transfection of F98 cells with constitutively active mutant of AKT (AKT/CA), however, did not significantly reverse Scutellaria-mediated inhibition of proliferation, indicating that Scutellaria flavonoids either directly inhibited Akt kinase activity or acted downstream of Akt. In vitro Akt kinase assay demonstrated that the SocL extract or wogonin could indeed bind to Akt and inhibit its kinase activity. This study provides the first in vivo evidence and mechanistic support for anti-glioma activity of Scutellaria flavonoids and has implications in potential usage of Scutellaria flavonoids in adjuvant therapy for malignant tumors, including gliomas.
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影响因子：
11.5
作者：
Miyashita, Katsuyoshi;Kawakami, Kazuyuki;Minamoto, Toshinari
通讯作者：
Minamoto, Toshinari
影响因子：
3.7
作者：
Korur S;Huber RM;Sivasankaran B;Petrich M;Morin P Jr;Hemmings BA;Merlo A;Lino MM
通讯作者：
Lino MM
影响因子：
6.4
作者：
Chung, Heekyoung;Jung, Youn -Mi;Kong, Gu
通讯作者：
Kong, Gu
影响因子：
1.6
作者：
Huang, Wen-Hsin;Lee, An-Rong;Yang, Ching-Huey
通讯作者：
Yang, Ching-Huey
影响因子：
4.8
作者：
Mathupala, SP;Parajuli, P;Sloan, AE
通讯作者：
Sloan, AE