Cell-based Drug and Health Products Development Research Unit, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Mar Drugs. 2019 Feb 11;17(2):109. doi: 10.3390/md17020109.
Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor. The discovery of novel compounds able to suppress CSCs and sensitize the chemotherapeutic response could be beneficial to the improvement of clinical outcomes. Herein, we report for the first time that 5--acetyl-renieramycin T isolated from the blue sponge sp. mediated lung cancer cell death via the induction of p53-dependent apoptosis. Importantly, 5--acetyl-renieramycin T induced the death of CSCs as represented by the CSC markers CD44 and CD133, while the stem cell transcription factor Nanog was also found to be dramatically decreased in 5--acetyl-renieramycin T-treated cells. We also found that such a CSC suppression was due to the ability of the compound to deplete the protein kinase B (AKT) signal. Furthermore, 5--acetyl-renieramycin T was able to significantly sensitize cisplatin-mediated apoptosis in the lung cancer cells. Together, the present research findings indicate that this promising compound from the marine sponge is a potential candidate for anti-cancer approaches.
肺癌是最严重的癌症之一，因为它几乎占全球癌症死亡人数的五分之一，而且发病率还在不断上升。由于癌细胞能够抵抗治疗和转移，癌症的治疗管理经常失败。最近的证据表明，当前治疗药物的反应不佳以及发生转移的能力是由肿瘤中的癌症干细胞 (CSC) 驱动的。发现能够抑制 CSC 并使化疗反应敏感的新型化合物可能有助于改善临床结果。在这里，我们首次报道，从蓝海绵 sp. 中分离出的 5--乙酰雷那霉素 T 通过诱导 p53 依赖性细胞凋亡介导肺癌细胞死亡。重要的是，5--乙酰雷那霉素 T 诱导了 CSC 死亡，这表现为 CSC 标志物 CD44 和 CD133 的表达降低，而干细胞转录因子 Nanog 也在 5--乙酰雷那霉素 T 处理的细胞中显著降低。我们还发现，这种 CSC 抑制是由于该化合物能够耗尽蛋白激酶 B (AKT) 信号。此外，5--乙酰雷那霉素 T 能够显著增强顺铂介导的肺癌细胞凋亡。总之，本研究结果表明，这种来自海洋海绵的有前途的化合物是一种潜在的抗癌方法的候选药物。
