King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model.
King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model.
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DOI：
10.7150/ijms.8096
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发表时间：
2014
影响因子：
3.6
通讯作者：
Tan NH
中科院分区：
文献类型：
--
作者：
Lee ML;Fung SY;Chung I;Pailoor J;Cheah SH;Tan NH
眼镜王蛇（Ophiophagus hannah）蛇毒L-氨基酸氧化酶（OH-LAAO）是一种热稳定酶，对人乳腺癌和肺癌的致瘤细胞有很强的抗增殖活性，但对非致瘤细胞无活性。我们进一步研究了其在体外和体内的抗肿瘤活性在人前列腺腺癌（PC-3）模型。OH-LAAO在体外孵育72 h后显示出对PC-3细胞的强效细胞毒性，IC 50为0.05 µg/mL。它诱导细胞凋亡，表现为半胱天冬酶-3/7裂解增加和膜联蛋白V染色细胞增加。为了检查其体内抗肿瘤活性，我们用腹膜内（i. p.）给予的1 μg/g OH-LAAO处理皮下植入免疫缺陷NU/NU（裸）小鼠中的PC-3肿瘤异种移植物。治疗8周后，与对照组相比，OH-LAAO治疗组PC-3肿瘤明显抑制（P <0.05）。肿瘤切片上的TUNEL染色分析显示LAAO处理的动物中凋亡细胞显著增加。两组重要脏器组织学检查与正常组织无明显差异，无明显组织损伤。在研究期间，给药也未引起小鼠体重的任何显著变化。这些观察结果表明，OH-LAAO细胞毒性作用可能是特定的肿瘤异种移植物和正常器官。鉴于其在体外和体内显示的有效抗肿瘤活性，眼镜王蛇毒液LAAO可能被开发用于治疗前列腺癌和其他实体瘤。
King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.
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影响因子：
5.5
作者：
Bava, Adriana;Gornati, Rosalba;Bernardini, Giovanni
通讯作者：
Bernardini, Giovanni
DOI：
10.1016/j.cbpc.2010.11.001
发表时间：
2011-03-01
影响因子：
3.9
作者：
Lee, Mui Li;Tan, Nget Hong;Sekaran, Shamala Devi
通讯作者：
Sekaran, Shamala Devi
影响因子：
3.2
作者：
Sun, LK;Yoshii, Y;Morine, N
通讯作者：
Morine, N
金环蛇蛇毒L-氨基酸氧化酶的纯化、表征及生物活性。
影响因子：
2.8
作者：
Wei, Ji-Fu;Yang, Hai-Wei;He, Shao-Heng
通讯作者：
He, Shao-Heng
影响因子：
3.2
作者：
Zhang, Liang;Cui, Li
通讯作者：
Cui, Li