Jung Young Yun, Um Jae-Young, Chinnathambi Arunachalam, Govindasamy Chandramohan, Sethi Gautam, Ahn Kwang Seok
Department of Science in Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Biology (Basel). 2022 Feb 25;11(3):366. doi: 10.3390/biology11030366.
Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.
利拉明（LEE）最近因其对黑色素瘤、乳腺癌和前列腺癌细胞的生长抑制作用而备受关注；然而，其对血液系统恶性肿瘤的影响仍不清楚。在此，我们首先研究了LEE对几种人类慢性髓性白血病（CML）细胞的细胞毒性作用。我们注意到LEE可刺激CML细胞的凋亡和自噬。此外，在LEE处理后，信号转导和转录激活因子5（STAT5）的组成性激活被显著抑制。此外，用小干扰RNA（siRNA）敲低STAT5可增加LEE诱导的凋亡以及自噬，并影响各种致癌蛋白的水平。因此，LEE对STAT5激活的靶向减轻可通过增强两种不同的细胞死亡途径来促进其多样的抗癌作用。
