Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

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

Organoantimony (III) Derivative Induces Necroptosis in Human Breast Cancer MDA-MB-231 Cells

Author(s): Yong-ping Liu*, Jian Lei, Ming-Ming Yin and Yi Chen*

Volume 22, Issue 13, 2022

Published on: 18 March, 2022

Page: [2448 - 2457] Pages: 10

DOI: 10.2174/1871520622666220118093643

Price: $65

Abstract

Aim: This study aimed to investigate the anticancer effect and the underlying mechanisms of organoantimony (III) fluoride on MDA-MB-231 human breast cancer cells.

Methods: Five cancer and one normal cell line were treated with an organoantimony (III) compound 6-cyclohexyl-12- fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (denoted as C4). The cell viability was detected by MTT assay. Induction of cell death was determined by Hoechst 33342/PI staining and Annexin-V/PI staining. The effect of C4 on the necroptotic relative protein was determined by Western blot analysis.

Results: Among the five cancer cell lines, C4 decreased the viability of MDA-MB-231, MCF-7 and A2780/cisR, and showed less toxicity on normal human embryonic kidney cells. In breast cancer cell line MDA-MB-231, the C4 treatment induced necrotic cell death as well as LDH release in a time- and dose-dependent manner. Moreover, C4 could increase the expression of phosphorylated RIPK3 and MLKL proteins. Overall, the C4 treatment resulted in the reduction of mitochondrial transmembrane potential and accumulation of ROS in MDA-MB-231 cells.

Conclusion: C4-induced necroptosis could be ascribed to glutathione depletion and ROS elevation in MDA-MB-231 cells. Our findings illustrate C4 to be a potential necroptosis inducer for breast cancer treatment.

Keywords: Metal complex, necroptosis inducer, anti-cancer, triple-negative breast cancer, ROS, oxidative stress.

« Previous Next »
Graphical Abstract

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Harbeck, N.; Gnant, M. Breast cancer. Lancet, 2017, 389(10074), 1134-1150.
[http://dx.doi.org/10.1016/S0140-6736(16)31891-8] [PMID: 27865536]
[3]
Pondé, N.F.; Zardavas, D.; Piccart, M. Progress in adjuvant systemic therapy for breast cancer. Nat. Rev. Clin. Oncol., 2019, 16(1), 27-44.
[http://dx.doi.org/10.1038/s41571-018-0089-9] [PMID: 30206303]
[4]
Alkabban, F.M.; Ferguson, T. Breast Cancer; Treasure Island, FL, 2021.
[5]
Kim, C.; Gao, R.; Sei, E.; Brandt, R.; Hartman, J.; Hatschek, T.; Crosetto, N.; Foukakis, T.; Navin, N.E. Chemoresistance evolution in triple-negative breast cancer deline-ated by single-cell sequencing. Cell, 2018, 173(4), 879-893.e13.
[http://dx.doi.org/10.1016/j.cell.2018.03.041] [PMID: 29681456]
[6]
Yin, L.; Duan, J.J.; Bian, X.W.; Yu, S.C. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res., 2020, 22(1), 61.
[http://dx.doi.org/10.1186/s13058-020-01296-5] [PMID: 32517735]
[7]
Hickey, T.E.; Selth, L.A.; Chia, K.M.; Laven-Law, G.; Milioli, H.H.; Roden, D.; Jindal, S.; Hui, M.; Finlay-Schultz, J.; Ebrahimie, E.; Birrell, S.N.; Stelloo, S.; Iggo, R.; Alexandrou, S.; Caldon, C.E.; Abdel-Fatah, T.M.; Ellis, I.O.; Zwart, W.; Palmieri, C.; Sartorius, C.A.; Swarbrick, A.; Lim, E.; Carroll, J.S.; Tilley, W.D. The androgen re-ceptor is a tumor suppressor in estrogen receptor-positive breast cancer. Nat. Med., 2021, 27(2), 310-320.
[http://dx.doi.org/10.1038/s41591-020-01168-7] [PMID: 33462444]
[8]
Tang, D.; Kang, R.; Berghe, T.V.; Vandenabeele, P.; Kroemer, G. The molecular machinery of regulated cell death. Cell Res., 2019, 29(5), 347-364.
[http://dx.doi.org/10.1038/s41422-019-0164-5] [PMID: 30948788]
[9]
Tonnus, W.; Meyer, C.; Paliege, A.; Belavgeni, A.; von Mässenhausen, A.; Bornstein, S.R.; Hugo, C.; Becker, J.U.; Linkermann, A. The pathological features of regulated necrosis. J. Pathol., 2019, 247(5), 697-707.
[http://dx.doi.org/10.1002/path.5248] [PMID: 30714148]
[10]
Galluzzi, L.; Kepp, O.; Chan, F.K.; Kroemer, G. Necroptosis: Mechanisms and Relevance to Disease. Annu. Rev. Pathol., 2017, 12, 103-130.
[http://dx.doi.org/10.1146/annurev-pathol-052016-100247] [PMID: 27959630]
[11]
Su, Z.; Yang, Z.; Xie, L.; DeWitt, J.P.; Chen, Y. Cancer therapy in the necroptosis era. Cell Death Differ., 2016, 23(5), 748-756.
[http://dx.doi.org/10.1038/cdd.2016.8] [PMID: 26915291]
[12]
Najafov, A.; Chen, H.; Yuan, J. Necroptosis and cancer. Trends Cancer, 2017, 3(4), 294-301.
[http://dx.doi.org/10.1016/j.trecan.2017.03.002] [PMID: 28451648]
[13]
Gong, Y.; Fan, Z.; Luo, G.; Yang, C.; Huang, Q.; Fan, K.; Cheng, H.; Jin, K.; Ni, Q.; Yu, X.; Liu, C. The role of necroptosis in cancer biology and therapy. Mol. Cancer, 2019, 18(1), 100.
[http://dx.doi.org/10.1186/s12943-019-1029-8] [PMID: 31122251]
[14]
Sprooten, J.; De Wijngaert, P.; Vanmeerbeerk, I.; Martin, S.; Vangheluwe, P.; Schlenner, S.; Krysko, D.V.; Parys, J.B.; Bultynck, G.; Vandenabeele, P.; Garg, A.D. Necrop-tosis in immuno-oncology and cancer immunotherapy. Cells, 2020, 9(8), E1823.
[http://dx.doi.org/10.3390/cells9081823] [PMID: 32752206]
[15]
Adeyemi, J.O.; Onwudiwe, D.C. Chemistry and some biological potential of bismuth and antimony dithiocarbamate complexes. Molecules, 2020, 25(2), E305.
[http://dx.doi.org/10.3390/molecules25020305] [PMID: 31940910]
[16]
Müller, S.; Miller, W.H., Jr; Dejean, A. Trivalent antimonials induce degradation of the PML-RAR oncoprotein and reorganization of the promyelocytic leukemia nuclear bodies in acute promyelocytic leukemia NB4 cells. Blood, 1998, 92(11), 4308-4316.
[http://dx.doi.org/10.1182/blood.V92.11.4308] [PMID: 9834237]
[17]
Ndagi, U.; Mhlongo, N.; Soliman, M.E. Metal complexes in cancer therapy - an update from drug design perspective. Drug Des. Devel. Ther., 2017, 11, 599-616.
[http://dx.doi.org/10.2147/DDDT.S119488] [PMID: 28424538]
[18]
Anthony, E.J.; Bolitho, E.M.; Bridgewater, H.E.; Carter, O.W.L.; Donnelly, J.M.; Imberti, C.; Lant, E.C.; Lermyte, F.; Needham, R.J.; Palau, M.; Sadler, P.J.; Shi, H.; Wang, F.X.; Zhang, W.Y.; Zhang, Z. Metallodrugs are unique: opportunities and challenges of discovery and development. Chem. Sci. (Camb.), 2020, 11(48), 12888-12917.
[http://dx.doi.org/10.1039/D0SC04082G] [PMID: 34123239]
[19]
Diederich, M.; Cerella, C. Non-canonical programmed cell death mechanisms triggered by natural compounds. Semin Cancer Biol, 2016, 40, 414-34.
[http://dx.doi.org/10.1016/j.semcancer.2016.06.001]
[20]
Huang, R.; Wallqvist, A.; Covell, D.G. Anticancer metal compounds in NCI’s tumor-screening database: putative mode of action. Biochem. Pharmacol., 2005, 69(7), 1009-1039.
[http://dx.doi.org/10.1016/j.bcp.2005.01.001] [PMID: 15763539]
[21]
Hsu, S.K.; Chang, W.T.; Lin, I.L.; Chen, Y.F.; Padalwar, N.B.; Cheng, K.C.; Teng, Y.N.; Wang, C.H.; Chiu, C.C. The role of necroptosis in ROS-mediated cancer therapies and its promising applications. Cancers (Basel), 2020, 12(8), E2185.
[http://dx.doi.org/10.3390/cancers12082185] [PMID: 32764483]
[22]
Suntharalingam, K.; Awuah, S.G.; Bruno, P.M.; Johnstone, T.C.; Wang, F.; Lin, W.; Zheng, Y.R.; Page, J.E.; Hemann, M.T.; Lippard, S.J. Necroptosis-inducing rhenium(V) oxo complexes. J. Am. Chem. Soc., 2015, 137(8), 2967-2974.
[http://dx.doi.org/10.1021/ja511978y] [PMID: 25698398]
[23]
Xiong, K.; Qian, C.; Yuan, Y.; Wei, L.; Liao, X.; He, L.; Rees, T.W.; Chen, Y.; Wan, J.; Ji, L.; Chao, H. Necroptosis induced by ruthenium(II) complexes as dual catalytic inhibitors of topoisomerase I/II. Angew. Chem. Int. Ed. Engl., 2020, 59(38), 16631-16637.
[http://dx.doi.org/10.1002/anie.202006089] [PMID: 32533618]
[24]
Lei, J.; Liu, Y.; Ou, Y.; Au, C.T.; Chen, Y.; Yin, S.F. Organoantimony(III) halide complexes with azastibocine framework as potential antitumor agents: Correlation between cytotoxic activity and N→Sb inter-coordination. Eur. J. Med. Chem., 2019, 177, 350-361.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.054] [PMID: 31158749]
[25]
Xie, X.; Zhao, Y.; Ma, C.Y.; Xu, X.M.; Zhang, Y.Q.; Wang, C.G.; Jin, J.; Shen, X.; Gao, J.L.; Li, N.; Sun, Z.J.; Dong, D.L. Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway. Br. J. Pharmacol., 2015, 172(15), 3929-3943.
[http://dx.doi.org/10.1111/bph.13184] [PMID: 25953698]
[26]
Badisa, R.B.; Darling-Reed, S.F.; Joseph, P.; Cooperwood, J.S.; Latinwo, L.M.; Goodman, C.B. Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells. Anticancer Res., 2009, 29(8), 2993-2996.
[PMID: 19661306]
[27]
Shen, F.; Pan, X.; Li, M.; Chen, Y.; Jiang, Y.; He, J. Pharmacological inhibition of necroptosis promotes human breast cancer cell proliferation and metastasis. OncoTargets Ther., 2020, 13, 3165-3176.
[http://dx.doi.org/10.2147/OTT.S246899] [PMID: 32368076]
[28]
Shahsavari, Z.; Karami-Tehrani, F.; Salami, S.; Ghasemzadeh, M. RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. Tumour Biol., 2016, 37(4), 4479-4491.
[http://dx.doi.org/10.1007/s13277-015-4258-5] [PMID: 26496737]
[29]
Golbaghi, G.; Castonguay, A. Rationally designed ruthenium complexes for breast cancer therapy. Molecules, 2020, 25(2), E265.
[http://dx.doi.org/10.3390/molecules25020265] [PMID: 31936496]
[30]
Babak, M.V.; Chong, K.R.; Rapta, P.; Zannikou, M.; Tang, H.M.; Reichert, L.; Chang, M.R.; Kushnarev, V.; Heffeter, P.; Meier-Menches, S.M.; Lim, Z.C.; Yap, J.Y.; Casini, A.; Balyasnikova, I.V.; Ang, W.H. Interfering with metabolic profile of triple-negative breast cancers using rationally designed metformin prodrugs. Angew. Chem. Int. Ed. Engl., 2021, 60(24), 13405-13413.
[http://dx.doi.org/10.1002/anie.202102266] [PMID: 33755286]
[31]
Belizário, J.; Vieira-Cordeiro, L.; Enns, S. Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediators Inflamm., 2015, 2015, 128076.
[http://dx.doi.org/10.1155/2015/128076] [PMID: 26491219]
[32]
Chen, J.; Kos, R.; Garssen, J.; Redegeld, F. Molecular insights into the mechanism of necroptosis: the necrosome as a potential therapeutic target. Cells, 2019, 8(12), E1486.
[http://dx.doi.org/10.3390/cells8121486] [PMID: 31766571]
[33]
Li, Y.; Bai, H.; Wang, H.; Shen, Y.; Tang, G.; Ping, Y. Reactive oxygen species (ROS)-responsive nanomedicine for RNAi-based cancer therapy. Nanoscale, 2017, 10(1), 203-214.
[http://dx.doi.org/10.1039/C7NR06689A] [PMID: 29210417]
[34]
Yang, B.; Chen, Y.; Shi, J. Reactive oxygen species (ROS)-based nanomedicine. Chem. Rev., 2019, 119(8), 4881-4985.
[http://dx.doi.org/10.1021/acs.chemrev.8b00626] [PMID: 30973011]
[35]
Zhang, Y.; Su, S.S.; Zhao, S.; Yang, Z.; Zhong, C.Q.; Chen, X.; Cai, Q.; Yang, Z.H.; Huang, D.; Wu, R.; Han, J. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat. Commun., 2017, 8, 14329.
[http://dx.doi.org/10.1038/ncomms14329] [PMID: 28176780]
[36]
Chen, Y.; Yu, K.; Tan, N.Y.; Qiu, R.H.; Liu, W.; Luo, N.L.; Tong, L.; Au, C.T.; Luo, Z.Q.; Yin, S.F. Synthesis, characterization and anti-proliferative activity of heterocy-clic hypervalent organoantimony compounds. Eur. J. Med. Chem., 2014, 79, 391-398.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.026] [PMID: 24747750]
[37]
Bock, F.J.; Tait, S.W.G. Mitochondria as multifaceted regulators of cell death. Nat. Rev. Mol. Cell Biol., 2020, 21(2), 85-100.
[http://dx.doi.org/10.1038/s41580-019-0173-8] [PMID: 31636403]
[38]
Moro, L. Mitochondria at the crossroads of physiology and pathology. J. Clin. Med., 2020, 9(6), E1971.
[http://dx.doi.org/10.3390/jcm9061971] [PMID: 32599695]
[39]
Ashkenazi, A.; Salvesen, G. Regulated cell death: signaling and mechanisms. Annu. Rev. Cell Dev. Biol., 2014, 30, 337-356.
[http://dx.doi.org/10.1146/annurev-cellbio-100913-013226] [PMID: 25150011]

Rights & Permissions Print Cite
Article Metrics
25
1
© 2024 Bentham Science Publishers | Privacy Policy