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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Analysis of Comparative Proteomic and Potent Targets of Peniciketal A in Human Acute Monocytic Leukemia

Author(s): Xue Gao, Yuming Zhou, Hongliu Sun, Desheng Liu, Jing Zhang, Junru Zhang, Weizhong Liu* and Xiaohong Pan*

Volume 19, Issue 4, 2019

Page: [515 - 527] Pages: 13

DOI: 10.2174/1871520619666190212124339

Price: $65

Abstract

Background: Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control group on human acute monocytic leukemia cell line THP-1.

Methods: The DEPs were analyzed by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label. The function and feature of the identified proteins were analyzed by the bioinformatic analysis. Western blotting was used to evaluate protein expression.

Results: The DEPs were primarily sub located in the cytoplasm and the nucleus by regulating 21 pathways enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, we preliminarily demonstrated that glucose-6-phosphate 1-dehydrogenase (G6PD), prolow-density lipoprotein receptor-related protein 1 (LRP1) and Calreticulin (CALR) might be the potent targets of Pe-A on death induction of THP-1 cells.

Conclusion: Collectively, this study not only provides a global proteomic profile as the supplementary data of our previous studies but also provides interesting information that Pe-A may exert more bio-activities.

Keywords: Peniciketal A, LS-MS/MS, proteomic analysis, apoptosis, autophagy, monocytic leukemia.

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[1]
Liu, W.Z.; Ma, L.Y.; Liu, D.S.; Huang, Y.L.; Wang, C.H.; Shi, S.S.; Pan, X.H.; Song, X.D.; Zhu, R.X. Peniciketals A-C, new spiroketals from saline soil derived Penicillium raistrichii. Org. Lett., 2014, 16(1), 90-93.
[2]
Gao, X.; Zhou, Y.; Sun, H.; Liu, D.; Zhang, J.; Zhang, J.; Liu, W.; Pan, X. Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia. Toxicol. Appl. Pharmacol., 2019, 366, 1-9.
[3]
Gao, X.; Zhou, Y.; Zheng, X.; Sun, H.; Zhang, J.; Liu, W.; Pan, X. Peniciketal, A. A novel spiroketal compound, exerts anticancer effects by inhibiting cell proliferation, migration and invasion of A549 lung cancer cells. Anticancer. Agents Med. Chem., 2018, 18(11), 1573-1581.
[4]
Degterev, A.; Boyce, M.; Yuan, J. A decade of caspases. Oncogene, 2003, 22(53), 8543-8567.
[5]
Thornberry, N.A. Caspases: a decade of death research. Cell Death Differ., 1999, 6(11), 1023-1027.
[6]
Shibutani, S.T.; Saitoh, T.; Nowag, H.; Munz, C.; Yoshimori, T. Autophagy and autophagy-related proteins in the immune system. Nat. Immunol., 2015, 16(10), 1014-1024.
[7]
El-Khattouti, A.; Selimovic, D.; Haikel, Y.; Hassan, M. Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer. J. Cell Death, 2013, 6, 37-55.
[8]
Chaabane, W.; User, S.D.; El-Gazzah, M.; Jaksik, R.; Sajjadi, E.; Rzeszowska-Wolny, J.; Los, M.J. Autophagy, apoptosis, mitoptosis and necrosis: Interdependence between those pathways and effects on cancer. Arch. Immunol. Ther. Exp. (Warsz.), 2013, 61(1), 43-58.
[9]
Cifani, P.; Kentsis, A. Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease. Proteomics, 2017, 17(1-2), 1600079.
[10]
Szklarczyk, D.; Franceschini, A.; Wyder, S.; Forslund, K.; Heller, D.; Huerta-Cepas, J.; Simonovic, M.; Roth, A.; Santos, A.; Tsafou, K.P.; Kuhn, M.; Bork, P.; Jensen, L.J.; von Mering, C. STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res., 2015, 43(Database issue), D447-D452.
[11]
Haferlach, T.; Schoch, C.; Schnittger, S.; Kern, W.; Loffler, H.; Hiddemann, W. Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): A study of 124 patients. Br. J. Haematol., 2002, 118(2), 426-431.
[12]
Villeneuve, P.; Kim, D.T.; Xu, W.; Brandwein, J.; Chang, H. The morphological subcategories of acute monocytic leukemia (M5a and M5b) share similar immunophenotypic and cytogenetic features and clinical outcomes. Leuk. Res., 2008, 32(2), 269-273.
[13]
Lomax, J. Get ready to GO! A biologist’s guide to the gene ontology. Brief. Bioinform., 2005, 6(3), 298-304.
[14]
Kanehisa, M.; Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30.
[15]
Yahiro, K.; Satoh, M.; Nakano, M.; Hisatsune, J.; Isomoto, H.; Sap, J.; Suzuki, H.; Nomura, F.; Noda, M.; Moss, J.; Hirayama, T. Low-density Lipoprotein Receptor-Related Protein-1 (LRP1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA. J. Biol. Chem., 2012, 287(37), 31104-31115.
[16]
Ambjorn, M.; Asmussen, J.W.; Lindstam, M.; Gotfryd, K.; Jacobsen, C.; Kiselyov, V.V.; Moestrup, S.K.; Penkowa, M.; Bock, E.; Berezin, V. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family. J. Neurochem., 2008, 104(1), 21-37.
[17]
Jiao, Y.; Ding, H.; Huang, S.; Liu, Y.; Sun, X.; Wei, W.; Ma, J.; Zheng, F. Bcl-XL and Mcl-1 upregulation by calreticulin promotes apoptosis resistance of fibroblast-like synoviocytes via activation of PI3K/Akt and STAT3 pathways in rheumatoid arthritis. Clin. Exp. Rheumatol., 2018, 36(5), 841-849.
[18]
Zhang, W.; Liu, Z.; Zhang, Y.; Bao, Q.; Wu, W.; Huang, H.; Liu, X. Silencing calreticulin gene might protect cardiomyocytes from angiotensin II-induced apoptosis. Life Sci., 2018, 198, 119-127.
[19]
Ju, H.Q.; Lu, Y.X.; Wu, Q.N.; Liu, J.; Zeng, Z.L.; Mo, H.Y.; Chen, Y.; Tian, T.; Wang, Y.; Kang, T.B.; Xie, D.; Zeng, M.S.; Huang, P.; Xu, R.H. Disrupting G6PD-mediated redox homeostasis enhances chemosensitivity in colorectal cancer. Oncogene, 2017, 36(45), 6282-6292.
[20]
Wang, X.; Liu, H.; Zhang, X.; Li, X.; Gu, H.; Zhang, H.; Fan, R. G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma. Tumour Biol., 2016, 37(1), 781-789.
[21]
Xia, Y.; Xia, H.; Chen, D.; Liao, Z.; Yan, Y. Mechanisms of autophagy and apoptosis mediated by JAK2 signaling pathway after spinal cord injury of rats. Exp. Ther. Med., 2017, 14(2), 1589-1593.
[22]
Cernaj, I.E. Simultaneous dual targeting of Par-4 and G6PD: A promising new approach in cancer therapy? Quintessence of a literature review on survival requirements of tumor cells. Cancer Cell Int., 2016, 16, 87.

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