Kim Hyeon Jeong, Choi Ji Won, Ree Jin, Lim Jung Sik, Lee Jisun, Kim Jun Il, Thapa Samir Bahadur, Sohng Jae Kyung, Park Yong Il
Department of Biotechnology, Graduate School, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea.
Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea.
Life Sci. 2022 Jul 1;300:120495. doi: 10.1016/j.lfs.2022.120495. Epub 2022 Mar 24.
Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer with a high mortality rate. Glycosylation of phenolic compounds may increase water-solubility and pharmacological activities and reduce the toxicity of aglycones. This study aimed to evaluate and compare the anticancer effect of aloe emodin 3-O-glucoside (AE3G) and its aglycone, aloe emodin (AE), against NSCLC.
A human adenocarcinoma cell line (A549) and other human non-small cell lung carcinoma cell lines (NCI-H460 cells and NCI-H1299 cells) and BALB/c nu/nu xenograft mice harbouring A549 cells were used as the NSCLC models. Inhibition of cell migration, disruption of mitochondrial membrane potential (MMP), DNA fragmentation, and expression levels of apoptotic proteins were measured by western blot, wound healing assay, JC-1 staining, or TUNEL staining. Histopathological changes in tumour tissues were observed by H&E and TUNEL staining.
With no significant cytotoxicity against noncancerous cells (Vero cells), AE3G (5-50 μM) significantly and more effectively inhibited the growth, attachment, migration, Bcl-2 expression, and activation of MEK/ERK and Akt signalling proteins and induced cytochrome c release and Bax expression in A549 cells than AE. AE3G also significantly decreased the growth of other NSCLC cells, NCI-H460 cells and NCI-H1299 cells. AE3G suppressed the mRNA expression of matrix metalloproteinases, MMP2 and MMP9, and augmented the collapse of the mitochondrial MMP, cleavage of caspases (caspase 9, 8, and 3) and PARP, and DNA fragmentation. Intraperitoneal injection of AE3G (13 and 26 mg/kg/day) reduced the tumour volume and weight and induced apoptotic cell death in tumour tissues of xenograft NSCLC mice.
The present study demonstrated that AE3G significantly and more effectively diminished human NSCLC cell growth and migration by triggering mitochondria-dependent intrinsic apoptosis than AE, providing AE3G as a new potent candidate to prevent or treat human NSCLC.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，死亡率很高。酚类化合物的糖基化可能会增加其水溶性和药理活性，并降低苷元的毒性。本研究旨在评估和比较芦荟大黄素3 - O - 葡萄糖苷（AE3G）及其苷元芦荟大黄素（AE）对NSCLC的抗癌作用。
使用人腺癌细胞系（A549）以及其他人非小细胞肺癌细胞系（NCI - H460细胞和NCI - H1299细胞）和携带A549细胞的BALB/c nu/nu裸鼠作为NSCLC模型。通过蛋白质免疫印迹法、伤口愈合试验、JC - 1染色或TUNEL染色来检测细胞迁移的抑制、线粒体膜电位（MMP）的破坏、DNA片段化以及凋亡蛋白的表达水平。通过苏木精和伊红染色（H&E）以及TUNEL染色观察肿瘤组织的组织病理学变化。
AE3G（5 - 50 μM）对非癌细胞（Vero细胞）无明显细胞毒性，与AE相比，能显著且更有效地抑制A549细胞的生长、附着、迁移、Bcl - 2表达以及MEK/ERK和Akt信号蛋白的激活，并诱导细胞色素c释放和Bax表达。AE3G还能显著降低其他NSCLC细胞系NCI - H460细胞和NCI - H1299细胞的生长。AE3G抑制基质金属蛋白酶MMP2和MMP9的mRNA表达，并加剧线粒体MMP的崩溃、半胱天冬酶（半胱天冬酶9、8和3）和PARP的裂解以及DNA片段化。腹腔注射AE3G（13和26 mg/kg/天）可减小移植瘤NSCLC小鼠肿瘤组织的体积和重量，并诱导凋亡性细胞死亡。
本研究表明，与AE相比，AE3G通过触发线粒体依赖性内源性凋亡，能显著且更有效地减少人NSCLC细胞的生长和迁移，为预防或治疗人NSCLC提供了一种新的有效候选药物。
