Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung, 80424, Taiwan, Republic of China.
Doctoral Degree Program in Marine Biotechnology, Academia Sinica, No. 128, Section 2, Academia Rd, Nangang District, Taipei City, 11529, Taiwan, Republic of China.
Apoptosis. 2018 Jun;23(5-6):314-328. doi: 10.1007/s10495-018-1456-9.
Prodigiosin, a secondary metabolite isolated from marine Vibrio sp., has antimicrobial and anticancer properties. This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines. Moreover, prodigiosin with fluorescence signals was detected in the endoplasmic reticulum and found to induce excessive levels of autophagy. These findings were confirmed by observation of LC3 puncta formation and acridine orange staining. Furthermore, prodigiosin caused cell death by activating the JNK pathway and decreasing the AKT/mTOR pathway in glioblastoma cells. Moreover, we found that the autophagy inhibitor 3-methyladenine reversed prodigiosin induced autophagic cell death. These findings of this study suggest that prodigiosin induces autophagic cell death and apoptosis in glioblastoma cells.
灵菌红素是一种从海洋弧菌中分离出来的次级代谢产物，具有抗菌和抗癌特性。本研究探讨了灵菌红素在神经胶质瘤中的细胞死亡机制。多形性胶质母细胞瘤（GBM）是一种侵袭性中枢神经系统原发性癌症。尽管进行了治疗或标准治疗，胶质母细胞瘤患者的中位生存期约为 14.6 个月。本研究的结果清楚地表明，灵菌红素显著降低了 U87MG 和 GBM8401 人神经胶质瘤细胞系的细胞活力和神经球形成能力。此外，用荧光信号检测到灵菌红素在内质网中，并发现其诱导过度的自噬。通过观察 LC3 斑点形成和吖啶橙染色证实了这一发现。此外，灵菌红素通过激活 JNK 通路和降低神经胶质瘤细胞中的 AKT/mTOR 通路引起细胞死亡。此外，我们发现自噬抑制剂 3-甲基腺嘌呤逆转了灵菌红素诱导的自噬性细胞死亡。本研究的这些发现表明，灵菌红素诱导神经胶质瘤细胞发生自噬性细胞死亡和细胞凋亡。
