title: Differentiation-inducing and anti-proliferative activities of isoliquiritigenin and all-trans-retinoic acid on B16F0 melanoma cells: Mechanisms profiling by RNA-seq.
abstract: Melanoma is a cancer that arises from melanocytes, specialized pigmented cells that are found predominantly in the skin. The incidence of malignant melanoma has significantly increased over the last decade. With the development of therapy, the survival rate of some kind of cancer has been improved greatly. But the treatment of melanoma remains unsatisfactory. Much of melanoma's resistance to traditional chemotherapy is believed to arise intrinsically, by virtue of potent growth and cell survival-promoting genetic alteration. Therefore, significant attention has recently been focused on differentiation therapy, as well as differentiation inducer compounds. In previous study, we found isoliquiritigenin (ISL), a natural product extracted from licorice, could induce B16F0 melanoma cell differentiation. Here we investigated the transcriptional response of melanoma differentiation process induced by ISL and all-trans-retinoic acid (RA). Results showed that 390 genes involves in 201 biochemical pathways were differentially expressed in ISL treatment and 304 genes in 193 pathways in RA treatment. Differential expressed genes (DGEs, fold-change (FC)≥10) with the function of anti-proliferative and differentiation inducing indicated a loss of grade malignancy characteristic. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated glutathione metabolism, glycolysis/gluconeogenesis and pentose phosphate pathway were the top three relative pathway perturbed by ISL, and mitogen-activated protein kinase (MAPK) signaling pathway was the most important pathway in RA treatment. In the analysis of hierarchical clustering of DEGs, we discovered 72 DEGs involved in the process of drug action. We thought Cited1, Tgm2, Xaf1, Cd59a, Fbxo2, Adh7 may have critical role in the differentiation of melanoma. The evidence displayed herein confirms the critical role of reactive oxygen species (ROS) in melanoma pathobiology and provides evidence for future targets in the development of next-generation biomarkers and therapeutics.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Hao
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Han
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: sunsg@nwsuaf.edu.cn.
authors.forename: Shiguo
authors.initials: S
authors.lastname: Sun
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, China. Electronic address: zqsyt@sohu.com.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D047188:Chalcones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D010427:Pentose Phosphate Pathway; D059467:Transcriptome; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D014212:Tretinoin; C040920:isoliquiritigenin
keywords: All-trans-retinoic acid; Differentiation; Isoliquiritigenin; Melanoma; RNA-seq; ROS