Oncology Reports, 2015.

Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux

Uddin Md Nazim, Sang-Youel Park

Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a transmembrane cytokine that is a promising anticancer agent as it selectively induces apoptosis in various types of tumor cells. Autophagic flux, which includes the complete process of autophagy, and suppression of autophagic flux has been increasingly recognized as a favorable and novel therapeutic approach for cancer treatment. Here, we showed that genistein, a major isoflavone compound that exerts its anticancer properties by inhibiting tumor cell proliferation, can induce TRAIL-mediated apoptotic cell death in TRAIL‑resistant human adenocarcinoma A549 cells. Notably, genistein treatment led to a marked increase in the accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II and p62 protein levels. The combination of genistein and TRAIL increased LC3-II, p62, activated caspase-3 and activated caspase-8 accumulation, confirming the inhibition of autophagic flux. Taken together, our results revealed that genistein enhanced TRAIL-induced tumor cell death in TRAIL-resistant A549 adenocarcinoma cells by inhibiting autophagic flux.

雅典《肿瘤报道》，2015

金雀异黄素通过自噬潮的失活增强TRAIL-诱导的肿瘤细胞死亡
 尤丁 麦德 纳泽姆，朴尚永
生物安全研究所,兽医学院,全北国立大学,全州,Jeonbuk 561 - 756年,韩国

肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种跨膜细胞因子，它是一种有希望的抗癌剂，因为它可以选择性诱导各种肿瘤细胞的凋亡。包括自噬的完整过程和自噬通量的抑制，自噬通量已经越来越被认为是癌症治疗的有利和新颖的治疗方法。在这里，我们表明，通过抑制肿瘤细胞增殖而发挥其抗癌特性的主要异黄酮化合物染料木素可以在TRAIL抗性人腺癌A549细胞中诱导TRAIL介导的凋亡细胞死亡。值得注意的是，染料木素治疗导致微管相关蛋白1轻链3（LC3）-II和p62蛋白水平的积累显着增加。染料木黄酮和TRAIL的组合增加了LC3-II，p62，活化的caspase-3和活化的半胱天冬酶-8的积累，证实了自噬通量的抑制。总之，我们的研究结果表明，通过抑制自噬通量，染料木黄酮增强了TRAIL抗性A549腺癌细胞中TRAIL诱导的肿瘤细胞死亡。