Inhibits Cancer Cells Growth by Inducing G2/M Arrest

Overview

Journal Front Pharmacol

Date 2023 Apr 3

PMID 37007025

Authors

Jing Li

Hsi-Yuan Huang

Yang-Chi-Dung Lin

Huali Zuo

Yun Tang

Hsien-Da Huang

Affiliations

Soon will be listed here.

Abstract

(CR) is one of the most widely used traditional Chinese medicine (TCM) with anti-cancer effects. Analyzing transcriptomic responses of different human cell lines to TCM treatment is a promising approach to understand the unbiased mechanism of TCM. This study treated ten cancer cell lines with different CR concentrations, followed by mRNA sequencing. Differential expression (DE) analysis and gene set enrichment analysis (GSEA) were utilized to analyze transcriptomic data. Finally, the screening results were verified by experiments. Both DE and GSEA analysis suggested the Cell cycle pathway was the most perturbated pathway by CR across these cell lines. By analyzing the clinical significance and prognosis of G2/M related genes (PLK1, CDK1, CCNB1, and CCNB2) in various cancer tissues, we found that they were up-regulated in most cancer types, and their down-regulation showed better overall survival rates in cancer patients. Finally, experiments validation on A549, Hep G2, and HeLa cells suggested that CR can inhibit cell growth by suppressing the PLK1/CDK1/ Cyclin B axis. This is the first study to apply transcriptomic analysis to investigate the cancer cell growth inhibition of CR on various human cancer cell lines. The core effect of CR on ten cancer cell lines is to induce G2/M arrest by inhibiting the PLK1/CDK1/Cyclin B axis.

Citing Articles

Novel Camptothecin Derivative 9c with Enhanced Antitumor Activity via NSA2-EGFR-P53 Signaling Pathway.

Du F, Zhang A, Qi X, Yin R, Jiang T, Li J Int J Mol Sci. 2025; 26(5).

PMID: 40076615 PMC: 11900506. DOI: 10.3390/ijms26051987.

Impact of Linggui Zhugan decoction on microwave ablation outcomes and recurrence in liver cancer.

Huang R, Cui J World J Gastrointest Oncol. 2025; 17(2):101177.

PMID: 39958537 PMC: 11756010. DOI: 10.4251/wjgo.v17.i2.101177.

Elucidating the anti-cancer potential of essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations.

Mohanty D, Padhee S, Priyadarshini A, Champati B, Das P, Jena S Heliyon. 2024; 10(6):e28026.

PMID: 38533033 PMC: 10963383. DOI: 10.1016/j.heliyon.2024.e28026.

Nitidine chloride inhibits G2/M phase by regulating the p53/14-3-3 Sigma/CDK1 axis for hepatocellular carcinoma treatment.

Zhang B, Zhou B, Huang G, Huang J, Lin X, Li Z Heliyon. 2024; 10(1):e24012.

PMID: 38283241 PMC: 10818205. DOI: 10.1016/j.heliyon.2024.e24012.

References

Li Y, Liu X, Du A, Zhu X, Yu B . miR-203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes. J Cell Biochem. 2018; 120(4):6605-6613. DOI: 10.1002/jcb.27955. View

Xu H, Zhang Y, Liu Z, Chen T, Lv C, Tang S . ETCM: an encyclopaedia of traditional Chinese medicine. Nucleic Acids Res. 2018; 47(D1):D976-D982. PMC: 6323948. DOI: 10.1093/nar/gky987. View

Wang S, Sun X, An S, Sang F, Zhao Y, Yu Z . High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata () by UHPLC-Q-Exactive Orbitrap-MS. Molecules. 2021; 26(13). PMC: 8428211. DOI: 10.3390/molecules26133977. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Ge S, Son E, Yao R . iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinformatics. 2018; 19(1):534. PMC: 6299935. DOI: 10.1186/s12859-018-2486-6. View

Ye Z, Chen D, Zheng R, Chen H, Xu T, Wang C . Curcumin induced G2/M cycle arrest in SK-N-SH neuroblastoma cells through the ROS-mediated p53 signaling pathway. J Food Biochem. 2021; 45(9):e13888. DOI: 10.1111/jfbc.13888. View

Lamb J, Crawford E, Peck D, Modell J, Blat I, Wrobel M . The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006; 313(5795):1929-35. DOI: 10.1126/science.1132939. View

Hu S, Xu Y, Meng L, Huang L, Sun H . Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Exp Ther Med. 2018; 16(2):1266-1272. PMC: 6090267. DOI: 10.3892/etm.2018.6345. View

Myers J, von Lersner A, Robbins C, Sang Q . Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer. PLoS One. 2015; 10(12):e0145322. PMC: 4687717. DOI: 10.1371/journal.pone.0145322. View

10.

Hnit S, Yao M, Xie C, Ge G, Bi L, Jin S . Transcriptional regulation of G/M regulatory proteins and perturbation of G/M Cell cycle transition by a traditional Chinese medicine recipe. J Ethnopharmacol. 2020; 251:112526. DOI: 10.1016/j.jep.2019.112526. View

11.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A, Kim S . The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7. PMC: 3320027. DOI: 10.1038/nature11003. View

12.

Yang X, Kui L, Tang M, Li D, Wei K, Chen W . High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery. Front Genet. 2020; 11:19. PMC: 7013098. DOI: 10.3389/fgene.2020.00019. View

13.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

14.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

15.

Polaski J, Udy D, Escobar-Hoyos L, Askan G, Leach S, Ventura A . The origins and consequences of variants in pancreatic adenosquamous carcinoma. Elife. 2021; 10. PMC: 7846273. DOI: 10.7554/eLife.62209. View

16.

Fang S, Dong L, Liu L, Guo J, Zhao L, Zhang J . HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine. Nucleic Acids Res. 2020; 49(D1):D1197-D1206. PMC: 7779036. DOI: 10.1093/nar/gkaa1063. View

17.

Park G, Song H, Park S, Son H, Um Y, Kim H . Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells. BMC Complement Altern Med. 2018; 18(1):28. PMC: 5858136. DOI: 10.1186/s12906-018-2096-x. View

18.

Chakraborty P . Herbal genomics as tools for dissecting new metabolic pathways of unexplored medicinal plants and drug discovery. Biochim Open. 2018; 6:9-16. PMC: 5991880. DOI: 10.1016/j.biopen.2017.12.003. View

19.

Zhang L, Tao X, Fu Q, Ge C, Li R, Li Z . Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways. Oncol Rep. 2019; 42(5):1843-1855. PMC: 6775800. DOI: 10.3892/or.2019.7278. View

20.

Gao X, Wang Y, Li Y, Wang Y, Yan M, Sun H . Huganpian, a traditional chinese medicine, inhibits liver cancer growth in vitro and in vivo by inducing autophagy and cell cycle arrest. Biomed Pharmacother. 2019; 120:109469. DOI: 10.1016/j.biopha.2019.109469. View