Plumbagin induces apoptosis, cell cycle arrest, and inhibits protein synthesis in LoVo colon cancer cells: A proteomic analysis.

LoVo cell line anticancer effects colon cancer eukaryotic initiation factor label-free proteomics plumbagin

Journal

Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549

Informations de publication

Date de publication:
Nov 2023
Historique:
revised: 30 05 2023
received: 10 04 2023
accepted: 17 07 2023
pubmed: 10 8 2023
medline: 10 8 2023
entrez: 9 8 2023
Statut: ppublish

Résumé

Extracted from the roots of Plumbago zeylanica L., plumbagin is a natural naphthoquinone with potential as an anticancer compound. However, no studies have investigated its impact on LoVo (colon cancer) cells, and the specific mechanisms by which plumbagin exerts its anticancer effects remain to be established. The anticancer potential of plumbagin against LoVo cells was evaluated using a battery of assays, including MTT assay, clone formation assay, transwell chamber invasion assay, and wound-curing assay. Cell cycle analysis and cell apoptosis analysis were conducted to break down the anticancer impact of plumbagin on LoVo cells. A label-free proteomics technology was employed to investigate alterations in protein expression in LoVo cells treated with plumbagin. Our investigation indicated that plumbagin markedly inhibited the LoVo cells proliferation, and induced the apoptosis in LoVo cells, simultaneously induced G0/G1 phase cell cycle arrest. The LC-MS/MS proteomics assay revealed 78 proteins that were differentially expressed upon treatment with plumbagin. Bioinformatics and functional analyses indicated that these proteins were predominantly involved in protein synthesis and translation. Our findings revealed that multiple mechanisms are involved in the anticancer activity of plumbagin against LoVo cells, resulting in decreased cell viability. Proteomic analysis suggests that plumbagin may impede protein synthesis by reducing the expression of eukaryotic initiation factors. Our findings demonstrate that plumbagin exerts its anticancer activity against LoVo cells through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, cell cycle arrest, and disruption of protein synthesis. These results provide new insights into the therapeutic potential of plumbagin for colon cancer treatment.

Identifiants

pubmed: 37558615
doi: 10.1111/cbdd.14305
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1075-1084

Subventions

Organisme : Young Foundation of State Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region
ID : GXZYZ20210173
Organisme : Guangxi Young and Middle Aged Teachers' Basic Scientific Research Ability Improvement Project
ID : 2020KY07021
Organisme : The Research Fund Project of Zhejiang Chinese Medical University
ID : 2022YKJ02

Informations de copyright

© 2023 John Wiley & Sons Ltd.

Références

Andhale, N. B., Shahnawaz, M., & Ade, A. B. (2019). Fungal endophytes of Plumbago zeylanica L. enhances plumbagin content. Botanical Studies, 60(1), 21. https://doi.org/10.1186/s40529-019-0270-1
Athanasios, A., Charalampos, V., Vasileios, T., & Ashraf, G. M. (2017). Protein-protein interaction (PPI) network: Recent advances in drug discovery. Current Drug Metabolism, 18(1), 5-10. https://doi.org/10.2174/138920021801170119204832
Chen, X., Chen, J., Feng, W., Huang, W., Wang, G., Sun, M., Luo, X., Wang, Y., Nie, Y., Fan, D., Wu, K., & Xia, L. (2023). FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC. Theranostics, 13(4), 1401-1418. https://doi.org/10.7150/thno.82269
Fabbri, L., Chakraborty, A., Robert, C., & Vagner, S. (2021). The plasticity of mRNA translation during cancer progression and therapy resistance. Nature Reviews. Cancer, 21(9), 558-577. https://doi.org/10.1038/s41568-021-00380-y
Gao, S., Shi, Q., Zhou, X., Liu, X., & Yu, R. (2015). Plumbagin inhibits growth of gliomas in vivo via suppression of FOXM1 expression. Journal of Pharmacological Sciences, 128(3), 131-136. https://doi.org/10.1016/j.jphs.2015.06.005
Gene Ontology Consortium. (2015). Gene ontology consortium: Going forward. Nucleic Acids Research, 43(Database issue), D1049-D1056. https://doi.org/10.1093/nar/gku1179
Hao, P., Yu, J., Ward, R., Liu, Y., Hao, Q., An, S., & Xu, T. (2020). Eukaryotic translation initiation factors as promising targets in cancer therapy. Cell Communication and Signaling: CCS, 18(1), 175. https://doi.org/10.1186/s12964-020-00607-9
Jampasri, S., Reabroi, S., Tungmunnithum, D., Parichatikanond, W., & Pinthong, D. (2022). Plumbagin suppresses breast cancer progression by downregulating HIF-1α expression via a PI3K/Akt/mTOR independent pathway under hypoxic condition. Molecules, 27(17), 5716. https://doi.org/10.3390/molecules27175716
Kanehisa, M., & Goto, S. (2000). KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Research, 28(1), 27-30. https://doi.org/10.1093/nar/28.1.27
Li, Y., Gan, Y., Liu, J., Li, J., Zhou, Z., Tian, R., Sun, R., Liu, J., Xiao, Q., Li, Y., Lu, P., Peng, Y., Peng, Y., Shu, G., & Yin, G. (2022). Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer. Signal Transduction and Targeted Therapy, 7(1), 87. https://doi.org/10.1038/s41392-022-00902-6
Lin, Y., Chen, Y., Wang, S., Ma, J., Peng, Y., Yuan, X., Lv, B., Chen, W., & Wei, Y. (2019). Plumbagin induces autophagy and apoptosis of SMMC-7721 cells in vitro and in vivo. Journal of Cellular Biochemistry, 120(6), 9820-9830. https://doi.org/10.1002/jcb.28262
Liu, X., Cai, W., Niu, M., Chong, Y., Liu, H., Hu, W., Wang, D., Gao, S., Shi, Q., Hu, J., Zhou, X., & Yu, R. (2015). Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1. Journal of Neuro-Oncology, 121(3), 469-477. https://doi.org/10.1007/s11060-014-1664-2
Park, H., Ha, J., & Park, S. B. (2019). Label-free target identification in drug discovery via phenotypic screening. Current Opinion in Chemical Biology, 50, 66-72. https://doi.org/10.1016/j.cbpa.2019.02.006
Piazza, I., Beaton, N., Bruderer, R., Knobloch, T., Barbisan, C., Chandat, L., Sudau, A., Siepe, I., Rinner, O., de Souza, N., Picotti, P., & Reiter, L. (2020). A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes. Nature Communications, 11(1), 4200. https://doi.org/10.1038/s41467-020-18071-x
Pu, Z., Yang, F., Wang, L., Diao, Y., & Chen, D. (2021). Advancements of compounds targeting Wnt and Notch signalling pathways in the treatment of inflammatory bowel disease and colon cancer. Journal of Drug Targeting, 29(5), 507-519. https://doi.org/10.1080/1061186X.2020.1864741
Shahbazian, D., Roux, P. P., Mieulet, V., Cohen, M. S., Raught, B., Taunton, J., Hershey, J. W., Blenis, J., Pende, M., & Sonenberg, N. (2006). The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. The EMBO Journal, 25, 2781-2791. https://doi.org/10.1038/sj.emboj.7601166
Sidhu, H., & Capalash, N. (2022). Plumbagin downregulates UHRF1, p-Akt, MMP-2 and suppresses survival, growth and migration of cervical cancer CaSki cells. Toxicology In Vitro, 86, 105512. https://doi.org/10.1016/j.tiv.2022.105512
Sinha, S., Pal, K., Elkhanany, A., Dutta, S., Cao, Y., Mondal, G., Iyer, S., Somasundaram, V., Couch, F. J., Shridhar, V., Bhattacharya, R., Mukhopadhyay, D., & Srinivas, P. (2013). Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. International Journal of Cancer, 132(5), 1201-1212. https://doi.org/10.1002/ijc.27724
Skoda, A. M., Simovic, D., Karin, V., Kardum, V., Vranic, S., & Serman, L. (2018). The role of the hedgehog signaling pathway in cancer: A comprehensive review. Bosnian Journal of Basic Medical Sciences, 18(1), 8-20. https://doi.org/10.17305/bjbms.2018.2756
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660
Weinberg, B. A., & Marshall, J. L. (2019). Colon cancer in young adults: Trends and their implications. Current Oncology Reports, 21(1), 3. https://doi.org/10.1007/s11912-019-0756-8
Yin, Z., Zhang, J., Chen, L., Guo, Q., Yang, B., Zhang, W., & Kang, W. (2020). Anticancer effects and mechanisms of action of plumbagin: Review of research advances. BioMed Research International, 2020, 6940953. https://doi.org/10.1155/2020/6940953
Yoshida, G. J. (2020). Regulation of heterogeneous cancer-associated fibroblasts: The molecular pathology of activated signaling pathways. Journal of Experimental & Clinical Cancer Research, 39(1), 112. https://doi.org/10.1186/s13046-020-01611-0

Auteurs

Jianlong Shu (J)

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Kaijie Wang (K)

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Danya Zhao (D)

The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Yanlin Zhou (Y)

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.

Classifications MeSH