Login Register Cart 0
Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Effective Inhibition of Mitochondrial Metabolism by Cryptotanshinone in MDA-MB231 cells: A Proteomic Analysis

Author(s): Jiefeng Zhou, Qingcao Li, Haoran Wu, Shin-Han Tsai and Yu-Ting Yeh*

Volume 19, Issue 1, 2022

Published on: 08 February, 2021

Page: [20 - 29] Pages: 10

DOI: 10.2174/1570164618666210208144542

Price: $65

Abstract

Background: Triple-negative breast cancer (TNBC) is a subtype of invasive cancer in breast with the symptoms of unfavourable prognosis and limited targeted treatment options. Evidence of changes in the metabolic status of TNBC, characterised by increased glycolysis, mitochondrial oxidative phosphorylation, as well as production and utilization of tricarboxylic acid cycle intermediates.

Objective: The objective of this study is to investigate the proteins altered in cryptotanshinone treated MDA-MB-231 cells and explore the key pathways and specific molecular markers involved in cryptotanshinone treatment.

Methods: We use unlabeled quantitative proteomics to gain insight into the anticancer mechanism of cryptotanshinone on MDA-MB231 triple negative breast cancer cells. And flow cytometry was used to detect apoptosis and changes in cell mitochondrial membrane potential.

Results: We show that inhibiting the expression of electron transport chain complex proteins, also inhibits mitochondrial oxidative phosphorylation. Additionally, down-regulation of the ribosime biogenesis pathway was found to inhibit cell metabolism.

Conclusion: In summary, results show that cryptotanshinone can trigger rapid and irreversible apoptosis in MDA-MB-231 cells through effectively inhibiting cell metabolism.

Keywords: Cryptotanshinone, proteomic, breast cancer, MDA-MB-231, mitochondrial, TNBC.

« Previous Next »
Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442]
[2]
Sorlie, T.; Perou, C.M.; Tibshirani, R.; Aas, T.; Geisler, S.; Johnsen, H.; Hastie, T.; Eisen, M.B.; van de Rijn, M.; Jeffrey, S.S.; Thorsen, T.; Quist, H.; Matese, J.C.; Brown, P.O.; Botstein, D.; Lonning, P.E.; Borresen-Dale, A-L. Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications. Proc. Natl. Acad. Sci. USA, 2001, 98(19), 10869-10874.
[http://dx.doi.org/10.1073/pnas.191367098]
[3]
Vallejos, C.S.; Gómez, H.L.; Cruz, W.R.; Pinto, J.A.; Dyer, R.R.; Velarde, R.; Suazo, J.F.; Neciosup, S.P.; León, M.; de la Cruz, M.A.; Vigil, C.E. Breast Cancer Classification According to Immunohistochemistry Markers: Subtypes and Association With Clinicopathologic Variables in a Peruvian Hospital Database. Clin. Breast Cancer, 2010, 10(4), 294-300.
[http://dx.doi.org/10.3816/CBC.2010.n.038]
[4]
Lehmann, B.D.; Bauer, J.A.; Chen, X.; Sanders, M.E.; Chakravarthy, A.B.; Shyr, Y.; Pietenpol, J.A. Identification of Human Triple-Negative Breast Cancer Subtypes and Preclinical Models for Selection of Targeted Therapies. J. Clin. Invest., 2011, 121(7), 2750-2767.
[http://dx.doi.org/10.1172/JCI45014]
[5]
Burstein, M.D.; Tsimelzon, A.; Poage, G.M.; Covington, K.R.; Contreras, A.; Fuqua, S.A.W.; Savage, M.I.; Osborne, C.K.; Hilsenbeck, S.G.; Chang, J.C.; Mills, G.B.; Lau, C.C.; Brown, P.H. Comprehensive Genomic Analysis Identifies Novel Subtypes and Targets of Triple-Negative Breast Cancer. Clin. Cancer Res., 2015, 21(7), 1688-1698.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0432]
[6]
Stirzaker, C.; Zotenko, E.; Song, J.Z.; Qu, W.; Nair, S.S.; Locke, W.J.; Stone, A.; Armstong, N.J.; Robinson, M.D.; Dobrovic, A.; Avery-Kiejda, K.A.; Peters, K.M.; French, J.D.; Stein, S.; Korbie, D.J.; Trau, M.; Forbes, J.F.; Scott, R.J.; Brown, M.A.; Francis, G.D.; Clark, S.J. Methylome Sequencing in Triple-Negative Breast Cancer Reveals Distinct Methylation Clusters with Prognostic Value. Nat. Commun., 2015, 6(1), 5899.
[http://dx.doi.org/10.1038/ncomms6899]
[7]
Jerusalem, G.; Collignon, J.; Schroeder, H.; Lousberg, L. Triple-Negative Breast Cancer: Treatment Challenges and Solutions. Breast Cancer Targets Ther., 2016, 93
[http://dx.doi.org/10.2147/BCTT.S69488]
[8]
Teicher, B.A.; Linehan, W.M.; Helman, L.J. Targeting Cancer Metabolism. Clin. Cancer Res., 2012, 18(20), 5537-5545.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2587]
[9]
Guimaraes, J.C.; Zavolan, M. Patterns of Ribosomal Protein Expression Specify Normal and Malignant Human Cells. Genome Biol., 2016, 17(1), 236.
[http://dx.doi.org/10.1186/s13059-016-1104-z]
[10]
Hsieh, A.C.; Liu, Y.; Edlind, M.P.; Ingolia, N.T.; Janes, M.R.; Sher, A.; Shi, E.Y.; Stumpf, C.R.; Christensen, C.; Bonham, M.J.; Wang, S.; Ren, P.; Martin, M.; Jessen, K.; Feldman, M.E.; Weissman, J.S.; Shokat, K.M.; Rommel, C.; Ruggero, D. The Translational Landscape of MTOR Signalling Steers Cancer Initiation and Metastasis. Nature, 2012, 485(7396), 55-61.
[http://dx.doi.org/10.1038/nature10912]
[11]
Lamb, R.; Harrison, H.; Smith, D.L.; Townsend, P.A.; Jackson, T.; Ozsvari, B.; Martinez-Outschoorn, U.E.; Pestell, R.G.; Howell, A.; Lisanti, M.P.; Sotgia, F. Targeting Tumor-Initiating Cells: Eliminating Anabolic Cancer Stem Cells with Inhibitors of Protein Synthesis or by Mimicking Caloric Restriction. Oncotarget, 2015, 6(7), 4585-4601.
[http://dx.doi.org/10.18632/oncotarget.3278]
[12]
Mann, J. Natural Products in Cancer Chemotherapy: Past, Present and Future. Nat. Rev. Cancer, 2002, 2(2), 143-148.
[http://dx.doi.org/10.1038/nrc723]
[13]
Raman, V.; Aryal, U.K.; Hedrick, V.; Ferreira, R.M.; Fuentes Lorenzo, J.L.; Stashenko, E.E.; Levy, M.; Levy, M.M.; Camarillo, I.G. Proteomic Analysis Reveals That an Extract of the Plant Lippia Origanoides Suppresses Mitochondrial Metabolism in Triple-Negative Breast Cancer Cells. J. Proteome Res., 2018, 17(10), 3370-3383.
[http://dx.doi.org/10.1021/acs.jproteome.8b00255]
[14]
Qi, P.; Li, Y.; Liu, X.; Jafari, F.A.; Zhang, X.; Sun, Q.; Ma, Z. Cryptotanshinone Suppresses Non-Small Cell Lung Cancer via MicroRNA-146a-5p/EGFR Axis. Int. J. Biol. Sci., 2019, 15(5), 1072-1079.
[http://dx.doi.org/10.7150/ijbs.31277]
[15]
Ji, Y.; Liu, Y.; Xue, N.; Du, T.; Wang, L.; Huang, R.; Li, L.; Yan, C.; Chen, X. Cryptotanshinone Inhibits Esophageal Squamous-Cell Carcinoma in vitro and in vivo through the Suppression of STAT3 Activation. OncoTargets Ther., 2019, 12, 883-896.
[http://dx.doi.org/10.2147/OTT.S187777]
[16]
Zhang, W.; Yu, W.; Cai, G.; Zhu, J.; Zhang, C.; Li, S.; Guo, J.; Yin, G.; Chen, C.; Kong, L. A New Synthetic Derivative of Cryptotanshinone KYZ3 as STAT3 Inhibitor for Triple-Negative Breast Cancer Therapy. Cell Death Dis., 2018, 9(11), 1098.
[http://dx.doi.org/10.1038/s41419-018-1139-z]
[17]
Kingston, D.G.I. Modern Natural Products Drug Discovery and Its Relevance to Biodiversity Conservation. J. Nat. Prod., 2011, 74(3), 496-511.
[http://dx.doi.org/10.1021/np100550t]
[18]
Zheng, Z-G.; Xu, H.; Suo, S-S.; Xu, X-L.; Ni, M-W.; Gu, L-H.; Chen, W.; Wang, L-Y.; Zhao, Y.; Tian, B.; Hua, Y-J. The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer. Sci. Rep., 2016, 6(1), 26093.
[http://dx.doi.org/10.1038/srep26093]
[19]
P. Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic Type of Mechanism. Nature, 1961, 191(4784), 144-148.
[http://dx.doi.org/10.1038/191144a0]
[20]
Ly, J.D.; Grubb, D.R.; Lawen, A. The Mitochondrial Membrane Potential (Deltapsi(m)) in Apoptosis; an Update. Apoptosis, 2003, 8(2), 115-128.
[http://dx.doi.org/10.1023/a:1022945107762]
[21]
Holliday, D.L.; Speirs, V. Choosing the Right Cell Line for Breast Cancer Research. Breast Cancer Res., 2011, 13(4), 215.
[http://dx.doi.org/10.1186/bcr2889]
[22]
Bertram, R.; Gram Pedersen, M.; Luciani, D.S.; Sherman, A. A Simplified Model for Mitochondrial ATP Production. J. Theor. Biol., 2006, 243(4), 575-586.
[http://dx.doi.org/10.1016/j.jtbi.2006.07.019]
[23]
Kuntz, E.M.; Baquero, P.; Michie, A.M.; Dunn, K.; Tardito, S.; Holyoake, T.L.; Helgason, G.V.; Gottlieb, E. Targeting Mitochondrial Oxidative Phosphorylation Eradicates Therapy-Resistant Chronic Myeloid Leukemia Stem Cells. Nat. Med., 2017, 23(10), 1234-1240.
[http://dx.doi.org/10.1038/nm.4399]
[24]
Farge, T.; Saland, E.; de Toni, F.; Aroua, N.; Hosseini, M.; Perry, R.; Bosc, C.; Sugita, M.; Stuani, L.; Fraisse, M.; Scotland, S.; Larrue, C.; Boutzen, H.; Féliu, V.; Nicolau-Travers, M-L.; Cassant-Sourdy, S.; Broin, N.; David, M.; Serhan, N.; Sarry, A.; Tavitian, S.; Kaoma, T.; Vallar, L.; Iacovoni, J.; Linares, L.K.; Montersino, C.; Castellano, R.; Griessinger, E.; Collette, Y.; Duchamp, O.; Barreira, Y.; Hirsch, P.; Palama, T.; Gales, L.; Delhommeau, F.; Garmy-Susini, B.H.; Portais, J-C.; Vergez, F.; Selak, M.; Danet-Desnoyers, G.; Carroll, M.; Récher, C.; Sarry, J-E. Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism. Cancer Discov., 2017, 7(7), 716-735.
[http://dx.doi.org/10.1158/2159-8290.CD-16-0441]
[25]
Lee, K.; Giltnane, J.M.; Balko, J.M.; Schwarz, L.J.; Guerrero-Zotano, A.L.; Hutchinson, K.E.; Nixon, M.J.; Estrada, M.V.; Sánchez, V.; Sanders, M.E.; Lee, T.; Gómez, H.; Lluch, A.; Pérez-Fidalgo, J.A.; Wolf, M.M.; Andrejeva, G.; Rathmell, J.C.; Fesik, S.W.; Arteaga, C.L. MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation. Cell Metab., 2017, 26(4), 633-647.e7.
[http://dx.doi.org/10.1016/j.cmet.2017.09.009]
[26]
Bosc, C.; Selak, M.A.; Sarry, J.E. Resistance Is Futile: Targeting Mitochondrial Energetics and Metabolism to Overcome Drug Resistance in Cancer Treatment. Cell Metab., 2017, 26(5), 705-707.
[http://dx.doi.org/10.1016/j.cmet.2017.10.013]
[27]
Zhou, J.; Su, C-M.; Chen, H-A.; Du, S.; Li, C-W.; Wu, H.; Tsai, S-H.; Yeh, Y-T. Cryptanshinone Inhibits the Glycolysis and Inhibits Cell Migration Through PKM2/β-Catenin Axis in Breast Cancer. OncoTargets Ther., 2020, 13, 8629-8639.
[http://dx.doi.org/10.2147/OTT.S239134]
[28]
Murray, N.P.; Aedo, S.; Fuentealba, C.; Reyes, E.; Jacob, O. How Localized Is Pathologically Localized Prostate Cancer? The Use of Secondary Circulating Prostate Cells as a Marker of Minimal Residual Disease and Their Association with Patient Outcome. Türk Üroloji Dergisi. Turk. J. Urol., 2017, 43(4), 456-461.
[http://dx.doi.org/10.5152/tud.2017.60251]
[29]
Arthurs, C.; Murtaza, B.N.; Thomson, C.; Dickens, K.; Henrique, R.; Patel, H.R.H.; Beltran, M.; Millar, M.; Thrasivoulou, C.; Ahmed, A. Expression of Ribosomal Proteins in Normal and Cancerous Human Prostate Tissue. PLoS One, 2017, 12(10)e0186047
[http://dx.doi.org/10.1371/journal.pone.0186047]
[30]
Erol, A.; Acikgoz, E.; Guven, U.; Duzagac, F.; Turkkani, A.; Colcimen, N.; Oktem, G. Ribosome Biogenesis Mediates Antitumor Activity of Flavopiridol in CD44+/CD24- Breast Cancer Stem Cells. Oncol. Lett., 2017, 14(6), 6433-6440.
[http://dx.doi.org/10.3892/ol.2017.7029]

Rights & Permissions Print Cite
Article Metrics
39
2
© 2024 Bentham Science Publishers | Privacy Policy