Lei Gao1, Yongli Feng2, Chaochao Ge2, Xiaojuan Xu3, Senzhen Wang4, Xinna Li2, Kemeng Zhang5, Chaojie Wang2, Fujun Dai6, Songqiang Xie7. 1. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China; Joint International Research Laboratory of Food & Medicine Resource Function, Henan University, Kaifeng, 475004, Henan, China. 2. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China. 3. School of Pharmacy, Henan University, Kaifeng 475004, Henan, China. 4. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China; School of Life Sciences, Henan University, Kaifeng, 475004, Henan, China. 5. School of Life Sciences, Henan University, Kaifeng, 475004, Henan, China. 6. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China; School of Life Sciences, Henan University, Kaifeng, 475004, Henan, China. Electronic address: fjdwl@vip.henu.edu.cn. 7. School of Pharmacy, Henan University, Kaifeng 475004, Henan, China. Electronic address: xiesq@henu.edu.cn.
Abstract
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Metastasis is the major cause of death in patients with CRC. Lycorine, the phenanthridine alkaloid most commonly found in spp of the Amaryllidaceae family, has shown promising anticancer activities with minor side effects. However, the effects and the detailed mechanism of lycorine against metastasis of CRC remains unclear. STUDY DESIGN/ METHODS: The purpose of this study was to investigate the effects of lycorine on CRC and characterize the molecular mechanisms observed in lycorine-treated CRC cells using RNA-sequencing. MTT assay, colony formation assay, acridine orange/ethidium bromide (AO/EB) staining and Annexin V-FITC/Propidium iodide (PI) staining were conducted to examine the effects of lycorine on cell proliferation and apoptosis in CRC cells. RNA sequencing, real-time PCR assays and western blot were performed. Migration and invasion abilities of lycorine-treated CRC cells were investigated by wound healing and transwell invasion assays. The mouse CRC lung metastasis model was established and was used to detect the effect of lycorine on CRC in vivo. RESULTS: Our results demonstrated that lycorine inhibited the proliferation and colony formation of CRC cells in a concentration-dependent manner. AO/EB staining and Annexin V-FITC/PI staining showed that lycorine induced apoptosis in a concentration-dependent manner. Lycorine also reduced lung metastasis of CRC in vivo. Moreover, transcriptomic analysis suggested that lycorine regulated the expression of 3556 genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was implicated according to the differentially expressed genes (DEGs), and multiple pathways including those of mitogen-activated protein kinase (MAPK), relaxin, Ras, phosphatidylinositol 3‑kinase (PI3K)-protein kinase B (Akt) and Wnt/β-catenin were selected by functional enrichment analyses. Furthermore, based on transcriptomic analysis, we found that the tumor necrosis factor (TNF) pathway and endoplasmic reticulum stress were responsible for lycorine-induced apoptosis. CONCLUSIONS: These results obtained in this study demonstrated that lycorine has the potential to suppress CRC in vitro and in vivo through the lycorine-regulated multiple signaling pathways.
BACKGROUND:Colorectal cancer (CRC) is one of the most common malignancies worldwide. Metastasis is the major cause of death in patients with CRC. Lycorine, the phenanthridine alkaloid most commonly found in spp of the Amaryllidaceae family, has shown promising anticancer activities with minor side effects. However, the effects and the detailed mechanism of lycorine against metastasis of CRC remains unclear. STUDY DESIGN/ METHODS: The purpose of this study was to investigate the effects of lycorine on CRC and characterize the molecular mechanisms observed in lycorine-treated CRC cells using RNA-sequencing. MTT assay, colony formation assay, acridine orange/ethidium bromide (AO/EB) staining and Annexin V-FITC/Propidium iodide (PI) staining were conducted to examine the effects of lycorine on cell proliferation and apoptosis in CRC cells. RNA sequencing, real-time PCR assays and western blot were performed. Migration and invasion abilities of lycorine-treated CRC cells were investigated by wound healing and transwell invasion assays. The mouse CRC lung metastasis model was established and was used to detect the effect of lycorine on CRC in vivo. RESULTS: Our results demonstrated that lycorine inhibited the proliferation and colony formation of CRC cells in a concentration-dependent manner. AO/EB staining and Annexin V-FITC/PI staining showed that lycorine induced apoptosis in a concentration-dependent manner. Lycorine also reduced lung metastasis of CRC in vivo. Moreover, transcriptomic analysis suggested that lycorine regulated the expression of 3556 genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was implicated according to the differentially expressed genes (DEGs), and multiple pathways including those of mitogen-activated protein kinase (MAPK), relaxin, Ras, phosphatidylinositol 3‑kinase (PI3K)-protein kinase B (Akt) and Wnt/β-catenin were selected by functional enrichment analyses. Furthermore, based on transcriptomic analysis, we found that the tumor necrosis factor (TNF) pathway and endoplasmic reticulum stress were responsible for lycorine-induced apoptosis. CONCLUSIONS: These results obtained in this study demonstrated that lycorine has the potential to suppress CRC in vitro and in vivo through the lycorine-regulated multiple signaling pathways.
Authors: Veronique Mathieu; Breana Laguera; Marco Masi; Sara Adriana Dulanto; Tanner W Bingham; Lucas W Hernandez; David Sarlah; Antonio Evidente; Denis L J Lafontaine; Alexander Kornienko; Michelle A Lane Journal: Biomolecules Date: 2022-09-09