Head and neck cancer is associated with poor prognosis because of its highly metastatic nature. For the better management of head and neck cancer patients, it is very important to diagnose the cancer at an early stage, as well as to prevent the rapid spread of cancer either through direct invasion or lymphatic metastasis. In present study, the effect of dehydrocrenatidine, which is a beta-carboline alkaloid found in the medicinal plant Picrasma quassioides, on human head and neck cancer metastasis was investigated. The study results revealed the treatment of FaDu, SCC9, and SCC47 cells with 5, 10, and 20 μM of dehydrocrenatidine significantly decreased the motility, migration, and invasion of head and neck cancer cells. Moreover, the dehydrocrenatidine treatment significantly decreased the expression of MMP-2 and phosphorylation of ERK1/2 and JNK1/2. Additional experiments revealed that the cotreatment of dehydrocrenatidine with either ERK1/2 or JNK1/2 inhibitor caused further reduction in cancer cell motility and migration compared to that in dehydrocrenatidine treatment alone. Moreover, similar trend was observed in case of ERK1/2 and JNK1/2 phosphorylation and MMP-2 expression after the cotreatment. Taken together, the mechanism by which dehydrocrenatidine can decrease the phosphorylation of ERK1/2 and JNK1/2, follow decrease the expression of MMP-2 and inhibits head and neck cancer cells invasion and migration. This present study identifies dehydrocrenatidine as a potent antimetastatic agent that can be used clinically to improve head and neck cancer prognosis.

中文翻译：

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Dehydrocrenatidine 通过调节 JNK1/2 和 ERK1/2 通路抑制头颈癌细胞侵袭和迁移并降低 MMP-2 表达

由于其高度转移性，头颈癌与预后不良有关。为了更好地管理头颈癌患者，早期诊断癌症以及防止癌症通过直接侵袭或淋巴转移迅速扩散非常重要。在目前的研究中，dehydrocrenatidine 的作用是在药用植物Picrasma quassioides中发现的一种 β-咔啉生物碱，对人头颈癌转移进行了调查。研究结果显示，用 5、10 和 20 μM 脱氢克雷那丁处理 FaDu、SCC9 和 SCC47 细胞显着降低了头颈癌细胞的运动性、迁移和侵袭能力。此外，dehydrocrenatidine 处理显着降低了 MMP-2 的表达和 ERK1/2 和 JNK1/2 的磷酸化。额外的实验表明，与单独的脱氢克雷那丁治疗相比，脱氢克雷那丁与 ERK1/2 或 JNK1/2 抑制剂的共同治疗导致癌细胞运动和迁移进一步降低。此外，在共处理后，ERK1/2 和 JNK1/2 磷酸化和 MMP-2 表达也观察到类似的趋势。综合起来，脱氢克雷那丁降低ERK1/2和JNK1/2磷酸化，进而降低MMP-2表达，抑制头颈部癌细胞侵袭和迁移的机制。本研究确定脱氢克雷那替丁是一种有效的抗转移药物，可在临床上用于改善头颈癌的预后。