Department of Otorhinolaryngology- Head and Neck Surgery, Section of Experimental Oncology, University of Kiel Schleswig-Holstein, Kiel, 24105, Germany.
Mol Cancer. 2013 Feb 14;12:12. doi: 10.1186/1476-4598-12-12.
Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts.
Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient (SCID) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20).
Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 (JNK3) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase (MAPK)/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68 ng/kg to 83 ng/kg) while no tumor regression occurred in control animals.
These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.
从腔肠动物（珊瑚）Palythoa caribaeorum 中分离出的海洋毒素——石房蛤毒素（PTX）是已知最有效的非蛋白物质之一。它是一种非常复杂的分子，同时具有亲脂性和亲水性区域。本研究在一系列头颈部鳞状细胞癌（HNSCC）细胞系和异种移植瘤实验中对 PTX 的作用进行了研究。
采用细胞毒性、集落形成和酶抑制剂检测、RT-PCR 和 Northern Blotting 分析 PTX 处理后 HNSCC 细胞和正常上皮细胞的细胞活力和钠/钾转运 ATP 酶亚单位 alpha1（ATP1AL1）和 GAPDH 的基因表达。为进行异种移植实验，使用严重联合免疫缺陷（SCID）小鼠分析肿瘤消退情况。使用 One-Way Annova（SPSS vs20）对数据进行统计学分析。
与正常细胞相比，肿瘤细胞（PTX 的 LD50 为 1.5 至 3.5ng/ml）中观察到明显的毒性作用。PTX 影响肿瘤细胞中 LDH 的释放和钠/钾转运 ATP 酶亚单位 alpha1 基因的表达，表明细胞完整性丧失，主要是质膜丧失。此外，在癌细胞中发现 c-Jun N-末端激酶 3（JNK3）mRNA 表达强烈受到抑制，与 PTX 毒性增强相关，提示丝裂原激活蛋白激酶（MAPK）/JNK 信号通路在 HNSCC 细胞对 PTX 耐药的机制中发挥重要作用。在接种癌细胞的小鼠中，将 PTX 注射到异种移植瘤中，24 天内 75%的治疗动物（68ng/kg 至 83ng/kg 的 LD50）的肿瘤广泛破坏，而对照组动物的肿瘤未发生消退。
这些结果清楚地表明，PTX 对头颈部癌具有优先毒性，因此值得进一步研究其作用，这可能会扩展我们对头颈部癌症生物学的认识。
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