Organisms such as Apostichopus japonicus are a group of marine invertebrates that produce a variety of alkaloids with bioactivities. Many of these alkaloids have been proven to be effective anticancer drugs. In this study, the anticancer activities of 6-bromohypaphorine (6-BHP) isolated from red sea cucumber, A. japonicus, were investigated. The anticancer effects of 6-BHP against tumor cell lines A549, HT-29, B16F10, MCF-7, and Hep3B were evaluated. The structure of 6-BHP was determined by mass spectroscopy (MS), as well as nuclear magnetic resonance spectroscopy (NMR). In the bioactivity assay, 6-BHP attenuated survival rate of A549 cell line with an IC₅₀ value of (197.1 ± 7.4) μmol/L. Among the five cancer cell lines, 6-BHP showed the strongest anticancer activity against A549 than any other cell lines. The results of acridine orange-ethidium bromide and Hoechst 33342 staining showed that 6-bhp treatment mediated the formation of apoptotic body. In addition, 6-BHP down-regulated B-cell lymphoma-extra large (Bcl-xL), while up-regulated both Bcl-2-associated X protein (Bax) and caspase-3 in a dose- and time-dependent manner. We suggest that 6-BHP induces apoptosis via the mitochondria-mediated pathway. This is the first report on the isolation of 6-BHP from A. japonicus.

刺参等生物是一组海洋无脊椎动物，可产生多种具有生物活性的生物碱。许多这些生物碱已被证明是有效的抗癌药物。在这项研究中，研究了从红海参A. japonicus 中分离的 6-溴水合碱 (6-BHP) 的抗癌活性。评估了 6-BHP 对肿瘤细胞系 A549、HT-29、B16F10、MCF-7 和 Hep3B 的抗癌作用。6-BHP 的结构由质谱 (MS) 和核磁共振光谱 (NMR) 确定。在生物活性测定中，6-BHP 降低了 A549 细胞系的存活率，IC ₅₀(197.1 ± 7.4) μmol/L 的值。在五种癌细胞系中，6-BHP 对 A549 的抗癌活性比任何其他细胞系都强。吖啶橙-溴化乙锭和Hoechst 33342染色结果表明6-bhp处理介导了凋亡小体的形成。此外，6-BHP 下调 B 细胞淋巴瘤超大 (Bcl-xL)，同时以剂量和时间依赖性方式上调 Bcl-2 相关 X 蛋白 (Bax) 和 caspase-3 . 我们建议 6-BHP 通过线粒体介导的途径诱导细胞凋亡。这是从A. japonicus 中分离 6-BHP 的第一份报告。