The vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde induces aberrant mitotic progression and enhances radio-sensitivity accompanying suppression the expression of PLK1 in esophageal squamous cell carcinoma
The vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde induces aberrant mitotic progression and enhances radio-sensitivity accompanying suppression the expression of PLK1 in esophageal squamous cell carcinoma
复制标题
香草醛衍生物 6-溴-5-羟基-4-甲氧基苯甲醛可诱导食管鳞状细胞癌中异常的有丝分裂进展并增强放射敏感性，同时抑制 PLK1 的表达
DOI：
10.1016/j.taap.2018.04.021
复制
发表时间：
2018
影响因子：
3.8
通讯作者：
Shang Zeng Fu
中科院分区：
文献类型：
--
作者：
Gu Meng Meng;Li Ming;Gao Dexuan;Liu Lang Huan;Lang Yue;Yang Si Ming;Ou Hongling;Huang Bo;Zhou Ping Kun;Shang Zeng Fu
食管鳞状细胞癌是中国最常见的食管癌。由于化疗是晚期ESCC的标准临床干预措施，因此开发高效、低毒/无毒的药物对于改善患者的临床结局和预后至关重要。一种新的香兰素衍生物，6-溴-5-羟基-4-甲氧基苯甲醛（BVAN08），最近被报道在癌细胞中激活不同的细胞死亡途径。在这项研究中，我们证明BVAN08通过抑制PLK1（一种重要的有丝分裂激酶）的表达，对ESCC细胞（TE-1和ECA-109）具有有效的抗增殖作用。与此一致的是，BVAN08在ESCC细胞中诱导有丝分裂阻滞和染色体错位。在BVAN08处理的ESCC细胞中，中心体周围的微管成核也被破坏。此外，BVAN08通过延长DNA损伤修复，增强ESCC细胞的放射敏感性。这些发现强调了BVAN08在癌症治疗中的潜在价值，并证明了BVAN08诱导有丝分裂灾难和增强ESCC细胞放射敏感性的潜在机制。
Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase. Consistent with this, BVAN08 induces mitotic arrest and chromosomal misalignment in ESCC cells. The disruption of microtubule nucleation around centrosomes is also observed in BVAN08 treated ESCC cells. Furthermore, BVAN08 enhances radio-sensitivity of ESCC cells by prolonging DNA damage repair. These findings underscore the potential value of BVAN08 in cancer therapeutics and demonstrate the underlying mechanism by which BVAN08 induces mitotic catastrophe and enhances radio-sensitivity in ESCC cells.