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

Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cells

Author(s): Sathiavani Arikrishnan*, Jian Sheng Loh*, Xian Wei Teo, Faris bin Norizan, May Lee Low, Sau Har Lee, Jhi Biau Foo and Yin Sim Tor*

Volume 22, Issue 5, 2022

Published on: 08 July, 2021

Page: [999 - 1011] Pages: 13

DOI: 10.2174/1871520621666210708100019

Price: $65

Abstract

Background: The lack of specificity, severe side effects, and development of drug resistance have largely limited the use of platinum-based compounds in cancer treatment. Therefore, copper complexes have emerged as potential alternatives to platinum-based compounds.

Objective: Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer effects in HT-29 colorectal cancer cells.

Methods: Cytotoxic effects of ternary copper (II) complex in HT-29 cells was evaluated using MTT assay, Real-Time Cell Analysis (RTCA) and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry. Apoptosis induction was studied by Annexin V-FITC/Propidium Iodide (PI) staining and mitochondrial membrane potential analysis (JC-10 staining) using flow cytometry. Intracellular Reactive Oxygen Species (ROS) were detected by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by western blot analysis.

Results: Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 μM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP- 1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential disruption, and ROS production were observed.

Conclusion: Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.

Keywords: Copper complex, colorectal cancer, apoptosis, cell cycle arrest, caspase, p53.

« Previous Next »
Graphical Abstract

[1]
Dekker, E.; Tanis, P.J.; Vleugels, J.L.A.; Kasi, P.M.; Wallace, M.B. Colorectal cancer. Lancet, 2019, 394(10207), 1467-1480.
[http://dx.doi.org/10.1016/S0140-6736(19)32319-0] [PMID: 31631858]
[2]
Kuipers, E.J.; Grady, W.M.; Lieberman, D.; Seufferlein, T.; Sung, J.J.; Boelens, P.G.; van de Velde, C.J.H.; Watanabe, T. Colorectal cancer. Nat. Rev. Dis. Primers, 2015, 1, 15065.
[http://dx.doi.org/10.1038/nrdp.2015.65] [PMID: 27189416]
[3]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[4]
Armstrong-Gordon, E.; Gnjidic, D.; McLachlan, A.J.; Hosseini, B.; Grant, A.; Beale, P.J.; Wheate, N.J. Patterns of platinum drug use in an acute care setting: A retrospective study. J. Cancer Res. Clin. Oncol., 2018, 144(8), 1561-1568.
[http://dx.doi.org/10.1007/s00432-018-2669-6] [PMID: 29789926]
[5]
Loupakis, F.; Cremolini, C.; Masi, G.; Lonardi, S.; Zagonel, V.; Salvatore, L.; Cortesi, E.; Tomasello, G.; Ronzoni, M.; Spadi, R.; Zaniboni, A.; Tonini, G.; Buonadonna, A.; Amoroso, D.; Chiara, S.; Carlomagno, C.; Boni, C.; Allegrini, G.; Boni, L.; Falcone, A. Initial therapy with folfoxiri and bevacizumab for metastatic colorectal cancer. N. Engl. J. Med., 2014, 371(17), 1609-1618.
[http://dx.doi.org/10.1056/NEJMoa1403108] [PMID: 25337750]
[6]
Cremolini, C.; Loupakis, F.; Antoniotti, C.; Lupi, C.; Sensi, E.; Lonardi, S.; Mezi, S.; Tomasello, G.; Ronzoni, M.; Zaniboni, A.; Tonini, G.; Carlomagno, C.; Allegrini, G.; Chiara, S.; D’Amico, M.; Granetto, C.; Cazzaniga, M.; Boni, L.; Fontanini, G.; Falcone, A. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: Updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol., 2015, 16(13), 1306-1315.
[http://dx.doi.org/10.1016/S1470-2045(15)00122-9] [PMID: 26338525]
[7]
Tomasello, G.; Petrelli, F.; Ghidini, M.; Russo, A.; Passalacqua, R.; Barni, S. FOLFOXIRI plus bevacizumab as conversion therapy for patients with initially unresectable metastatic colorectal cancer: A systematic review and pooled analysis. JAMA Oncol., 2017, 3(7), e170278-e170278.
[http://dx.doi.org/10.1001/jamaoncol.2017.0278] [PMID: 28542671]
[8]
Sørensen, B.H.; Dam, C.S.; Stürup, S.; Lambert, I.H. Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells. J. Inorg. Biochem., 2016, 160, 287-295.
[http://dx.doi.org/10.1016/j.jinorgbio.2016.04.004] [PMID: 27112899]
[9]
Planells-Cases, R.; Lutter, D.; Guyader, C.; Gerhards, N.M.; Ullrich, F.; Elger, D.A.; Kucukosmanoglu, A.; Xu, G.; Voss, F.K.; Reincke, S.M.; Stauber, T.; Blomen, V.A.; Vis, D.J.; Wessels, L.F.; Brummelkamp, T.R.; Borst, P.; Rottenberg, S.; Jentsch, T.J. Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J., 2015, 34(24), 2993-3008.
[http://dx.doi.org/10.15252/embj.201592409] [PMID: 26530471]
[10]
Rottenberg, S.; Disler, C.; Perego, P. The rediscovery of platinum-based cancer therapy. Nat. Rev. Cancer, 2020, 2020
[http://dx.doi.org/10.1038/s41568-020-00308-y]
[11]
Krishnamoorthy, L.; Cotruvo, J.A., Jr; Chan, J.; Kaluarachchi, H.; Muchenditsi, A.; Pendyala, V.S.; Jia, S.; Aron, A.T.; Ackerman, C.M.; Wal, M.N.V.; Guan, T.; Smaga, L.P.; Farhi, S.L.; New, E.J.; Lutsenko, S.; Chang, C.J. Copper regulates cyclic-AMP-dependent lipolysis. Nat. Chem. Biol., 2016, 12(8), 586-592.
[http://dx.doi.org/10.1038/nchembio.2098] [PMID: 27272565]
[12]
Ishida, S.; Andreux, P.; Poitry-Yamate, C.; Auwerx, J.; Hanahan, D. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc. Natl. Acad. Sci. USA, 2013, 110(48), 19507-19512.
[http://dx.doi.org/10.1073/pnas.1318431110] [PMID: 24218578]
[13]
Tsang, T.; Posimo, J.M.; Gudiel, A.A.; Cicchini, M.; Feldser, D.M.; Brady, D.C. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat. Cell Biol., 2020, 22(4), 412-424.
[http://dx.doi.org/10.1038/s41556-020-0481-4] [PMID: 32203415]
[14]
Marzano, C.; Pellei, M.; Tisato, F.; Santini, C. Copper complexes as anticancer agents. Anticancer. Agents Med. Chem., 2009, 9(2), 185-211.
[http://dx.doi.org/10.2174/187152009787313837] [PMID: 19199864]
[15]
Brady, D.C.; Crowe, M.S.; Turski, M.L.; Hobbs, G.A.; Yao, X.; Chaikuad, A.; Knapp, S.; Xiao, K.; Campbell, S.L.; Thiele, D.J.; Counter, C.M. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature, 2014, 509(7501), 492-496.
[http://dx.doi.org/10.1038/nature13180] [PMID: 24717435]
[16]
Brady, D.C.; Crowe, M.S.; Greenberg, D.N.; Counter, C.M. Copper chelation inhibits brafv600e-driven melanomagenesis and counters resistance to BRAFV600E and MEK1/2 inhibitors. Cancer Res., 2017, 77(22), 6240-6252.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1190] [PMID: 28986383]
[17]
Xu, M.; Casio, M.; Range, D.E.; Sosa, J.A.; Counter, C.M. Copper chelation as targeted therapy in a mouse model of oncogenic BRAF-driven papillary thyroid cancer. Clin. Cancer Res., 2018, 24(17), 4271-4281.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3705] [PMID: 30065097]
[18]
Denoyer, D.; Masaldan, S.; La Fontaine, S.; Cater, M.A. Targeting copper in cancer therapy: ‘Copper that cancer’. Metallomics, 2015, 7(11), 1459-1476.
[http://dx.doi.org/10.1039/C5MT00149H] [PMID: 26313539]
[19]
Valko, M.; Jomova, K.; Rhodes, C.J.; Kuča, K.; Musílek, K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch. Toxicol., 2016, 90(1), 1-37.
[http://dx.doi.org/10.1007/s00204-015-1579-5] [PMID: 26343967]
[20]
Ishida, S.; McCormick, F.; Smith-McCune, K.; Hanahan, D. Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator. Cancer Cell, 2010, 17(6), 574-583.
[http://dx.doi.org/10.1016/j.ccr.2010.04.011] [PMID: 20541702]
[21]
Santini, C.; Pellei, M.; Gandin, V.; Porchia, M.; Tisato, F.; Marzano, C. Advances in copper complexes as anticancer agents. Chem. Rev., 2014, 114(1), 815-862.
[http://dx.doi.org/10.1021/cr400135x] [PMID: 24102434]
[22]
Wang, J.; Luo, C.; Shan, C.; You, Q.; Lu, J.; Elf, S.; Zhou, Y.; Wen, Y.; Vinkenborg, J.L.; Fan, J.; Kang, H.; Lin, R.; Han, D.; Xie, Y.; Karpus, J.; Chen, S.; Ouyang, S.; Luan, C.; Zhang, N.; Ding, H.; Merkx, M.; Liu, H.; Chen, J.; Jiang, H.; He, C. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation. Nat. Chem., 2015, 7(12), 968-979.
[http://dx.doi.org/10.1038/nchem.2381] [PMID: 26587712]
[23]
Mahendiran, D.; Amuthakala, S.; Bhuvanesh, N.S.P.; Kumar, R.S.; Rahiman, A.K. Copper complexes as prospective anticancer agents: In vitro and in vivo evaluation, selective targeting of cancer cells by DNA damage and S phase arrest. RSC Adv, 2018, 30, 16973-16990.
[24]
Abdel-Mohsen, M.A.; Abdel Malak, C.A.; Abou Yossef, M.A.; El-Shafey, E.S. Antitumor activity of copper (i)-nicotinate complex and autophagy modulation in hcc1806 breast cancer cells. Anticancer. Agents Med. Chem., 2017, 17(11), 1526-1536.
[http://dx.doi.org/10.2174/1871520617666170327144122] [PMID: 28356017]
[25]
Anbu, S.; Killivalavan, A.; Alegria, E.C.B.A.; Mathan, G.; Kandaswamy, M. Effect of 1,10-phenanthroline on DNA binding, DNA cleavage, cytotoxic and lactate dehydrogenase inhibition properties of Robson type macrocyclic dicopper(II) complex. J. Coord. Chem., 2013, 66(22), 3989-4003.
[http://dx.doi.org/10.1080/00958972.2013.858136]
[26]
Bortolotto, T.; Silva, P.P.; Neves, A.; Pereira-Maia, E.C.; Terenzi, H. Photoinduced DNA cleavage promoted by two copper(II) complexes of tetracyclines and 1,10-phenanthroline. Inorg. Chem., 2011, 50(21), 10519-10521.
[http://dx.doi.org/10.1021/ic201349s] [PMID: 21970295]
[27]
Cadavid-Vargas, J.F.; Leon, I.E.; Etcheverry, S.B.; Santi, E.; Torre, M.H.; Di Virgilio, A.L. Copper(II) complexes with saccharinate and glutamine as antitumor agents: Cytoand genotoxicity in human osteosarcoma cells. Anticancer. Agents Med. Chem., 2017, 17(3), 424-433.
[http://dx.doi.org/10.2174/1871520616666160513130204] [PMID: 27173967]
[28]
Hussain, A.; AlAjmi, M.F.; Rehman, M.T.; Amir, S.; Husain, F.M.; Alsalme, A.; Siddiqui, M.A.; AlKhedhairy, A.A.; Khan, R.A. Copper(II) complexes as potential anticancer and Nonsteroidal anti-inflammatory agents: In vitro and in vivo studies. Sci. Rep., 2019, 9(1), 5237.
[http://dx.doi.org/10.1038/s41598-019-41063-x] [PMID: 30918270]
[29]
Katarzyna, M.; Anna, S.; Zielinska-Blizniewska, H.; Ireneusz, M. An evaluation of the antioxidant and anticancer properties of complex compounds of copper (ii), platinum (ii), palladium (ii) and ruthenium (iii) for use in cancer therapy. Mini Rev. Med. Chem., 2018, 18(16), 1373-1381.
[http://dx.doi.org/10.2174/1389557518666180423145825] [PMID: 29692246]
[30]
Kostelidou, A.; Kalogiannis, S.; Begou, O-A.; Perdih, F.; Turel, I.; Psomas, G. Synthesis, structure and biological activity of copper(II) complexes with gatifloxacin. Polyhedron, 2016, 119, 359-370.
[http://dx.doi.org/10.1016/j.poly.2016.09.012]
[31]
Shi, X.; Chen, Z.; Wang, Y.; Guo, Z.; Wang, X. Hypotoxic copper complexes with potent anti-metastatic and anti-angiogenic activities against cancer cells. Dalton Trans., 2018, 47(14), 5049-5054.
[http://dx.doi.org/10.1039/C8DT00794B] [PMID: 29561011]
[32]
Fatfat, M.; Merhi, R.A.; Rahal, O.; Stoyanovsky, D.A.; Zaki, A.; Haidar, H.; Kagan, V.E.; Gali-Muhtasib, H.; Machaca, K. Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species. BMC Cancer, 2014, 14(1), 527.
[http://dx.doi.org/10.1186/1471-2407-14-527] [PMID: 25047035]
[33]
Low, M.L.; Chan, C.W.; Ng, P.Y.; Ooi, I.H.; Maah, M.J.; Chye, S.M.; Tan, K.W.; Ng, S.W.; Ng, C.H. Ternary and binary copper(II) complexes: Synthesis, characterization, ROS-inductive, proteasome inhibitory, and anticancer properties. J. Coord. Chem., 2017, 70(2), 223-241.
[http://dx.doi.org/10.1080/00958972.2016.1260711]
[34]
Reddy, P.R.; Shilpa, A.; Raju, N.; Raghavaiah, P. Synthesis, structure, DNA binding and cleavage properties of ternary amino acid Schiff base-phen/bipy Cu(II) complexes. J. Inorg. Biochem., 2011, 105(12), 1603-1612.
[http://dx.doi.org/10.1016/j.jinorgbio.2011.08.022] [PMID: 22071085]
[35]
Silva, P.P.; Guerra, W.; Silveira, J.N.; Ferreira, A.M.D.C.; Bortolotto, T.; Fischer, F.L.; Terenzi, H.; Neves, A.; Pereira-Maia, E.C. Two new ternary complexes of copper(II) with tetracycline or doxycycline and 1,10-phenanthroline and their potential as antitumoral: Cytotoxicity and DNA cleavage. Inorg. Chem., 2011, 50(14), 6414-6424.
[http://dx.doi.org/10.1021/ic101791r] [PMID: 21692452]
[36]
Galluzzi, L.; Vitale, I.; Aaronson, S.A.; Abrams, J.M.; Adam, D.; Agostinis, P.; Alnemri, E.S.; Altucci, L.; Amelio, I.; Andrews, D.W.; Annicchiarico-Petruzzelli, M.; Antonov, A.V.; Arama, E.; Baehrecke, E.H.; Barlev, N.A.; Bazan, N.G.; Bernassola, F.; Bertrand, M.J.M.; Bianchi, K.; Blagosklonny, M.V.; Blomgren, K.; Borner, C.; Boya, P.; Brenner, C.; Campanella, M.; Candi, E.; Carmona-Gutierrez, D.; Cecconi, F.; Chan, F.K.M.; Chandel, N.S.; Cheng, E.H.; Chipuk, J.E.; Cidlowski, J.A.; Ciechanover, A.; Cohen, G.M.; Conrad, M.; Cubillos-Ruiz, J.R.; Czabotar, P.E.; D’Angiolella, V.; Dawson, T.M.; Dawson, V.L.; De Laurenzi, V.; De Maria, R.; Debatin, K.M.; DeBerardinis, R.J.; Deshmukh, M.; Di Daniele, N.; Di Virgilio, F.; Dixit, V.M.; Dixon, S.J.; Duckett, C.S.; Dynlacht, B.D.; El-Deiry, W.S.; Elrod, J.W.; Fimia, G.M.; Fulda, S.; García-Sáez, A.J.; Garg, A.D.; Garrido, C.; Gavathiotis, E.; Golstein, P.; Gottlieb, E.; Green, D.R.; Greene, L.A.; Gronemeyer, H.; Gross, A.; Hajnoczky, G.; Hardwick, J.M.; Harris, I.S.; Hengartner, M.O.; Hetz, C.; Ichijo, H.; Jäättelä, M.; Joseph, B.; Jost, P.J.; Juin, P.P.; Kaiser, W.J.; Karin, M.; Kaufmann, T.; Kepp, O.; Kimchi, A.; Kitsis, R.N.; Klionsky, D.J.; Knight, R.A.; Kumar, S.; Lee, S.W.; Lemasters, J.J.; Levine, B.; Linkermann, A.; Lipton, S.A.; Lockshin, R.A.; López-Otín, C.; Lowe, S.W.; Luedde, T.; Lugli, E.; MacFarlane, M.; Madeo, F.; Malewicz, M.; Malorni, W.; Manic, G.; Marine, J.C.; Martin, S.J.; Martinou, J.C.; Medema, J.P.; Mehlen, P.; Meier, P.; Melino, S.; Miao, E.A.; Molkentin, J.D.; Moll, U.M.; Muñoz-Pinedo, C.; Nagata, S.; Nuñez, G.; Oberst, A.; Oren, M.; Overholtzer, M.; Pagano, M.; Panaretakis, T.; Pasparakis, M.; Penninger, J.M.; Pereira, D.M.; Pervaiz, S.; Peter, M.E.; Piacentini, M.; Pinton, P.; Prehn, J.H.M.; Puthalakath, H.; Rabinovich, G.A.; Rehm, M.; Rizzuto, R.; Rodrigues, C.M.P.; Rubinsztein, D.C.; Rudel, T.; Ryan, K.M.; Sayan, E.; Scorrano, L.; Shao, F.; Shi, Y.; Silke, J.; Simon, H.U.; Sistigu, A.; Stockwell, B.R.; Strasser, A.; Szabadkai, G.; Tait, S.W.G.; Tang, D.; Tavernarakis, N.; Thorburn, A.; Tsujimoto, Y.; Turk, B.; Vanden Berghe, T.; Vandenabeele, P.; Vander Heiden, M.G.; Villunger, A.; Virgin, H.W.; Vousden, K.H.; Vucic, D.; Wagner, E.F.; Walczak, H.; Wallach, D.; Wang, Y.; Wells, J.A.; Wood, W.; Yuan, J.; Zakeri, Z.; Zhivotovsky, B.; Zitvogel, L.; Melino, G.; Kroemer, G. Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018. Cell Death Differ., 2018, 25(3), 486-541.
[http://dx.doi.org/10.1038/s41418-017-0012-4] [PMID: 29362479]
[37]
Kim, I.W.; Lee, J.H.; Kwon, Y.N.; Yun, E.Y.; Nam, S.H.; Ahn, M.Y.; Kang, D.C.; Hwang, J.S. Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis. Int. J. Oncol., 2013, 43(2), 622-628.
[http://dx.doi.org/10.3892/ijo.2013.1973] [PMID: 23732481]
[38]
Chan, F.K.M.; Moriwaki, K.; De Rosa, M.J. Detection of necrosis by release of lactate dehydrogenase activity. Methods Mol. Biol., 2013, 979, 65-70.
[http://dx.doi.org/10.1007/978-1-62703-290-2_7] [PMID: 23397389]
[39]
Gholampour, M.; Ranjbar, S.; Edraki, N.; Mohabbati, M.; Firuzi, O.; Khoshneviszadeh, M. Click chemistry-assisted synthesis of novel aminonaphthoquinone-1,2,3-triazole hybrids and investigation of their cytotoxicity and cancer cell cycle alterations. Bioorg. Chem., 2019, 88102967
[http://dx.doi.org/10.1016/j.bioorg.2019.102967] [PMID: 31078767]
[40]
Gezici, S.; Şekeroğlu, N. Current perspectives in the application of medicinal plants against cancer: Novel therapeutic agents. Anticancer. Agents Med. Chem., 2019, 19(1), 101-111.
[http://dx.doi.org/10.2174/1871520619666181224121004] [PMID: 30582485]
[41]
Wang, K.; Gao, E. Recent advances in multinuclear complexes as potential anticancer and DNA binding agents. Anticancer. Agents Med. Chem., 2014, 14(1), 147-169.
[http://dx.doi.org/10.2174/18715206113139990313] [PMID: 23869783]
[42]
Zeng, L.; Chen, Y.; Liu, J.; Huang, H.; Guan, R.; Ji, L.; Chao, H. Ruthenium(ii) complexes with 2-phenylimidazo[4,5-f][1,10]phenanthroline derivatives that strongly combat cisplatin-resistant tumor cells. Sci. Rep., 2016, 6(1), 19449.
[http://dx.doi.org/10.1038/srep19449] [PMID: 26763798]
[43]
Foo, J.B.; Low, M.L.; Lim, J.H.; Lor, Y.Z.; Zainol Abidin, R.; Eh Dam, V.; Abdul Rahman, N.; Beh, C.Y.; Chan, L.C.; How, C.W.; Tor, Y.S.; Saiful Yazan, L. Copper complex derived from S-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell. Biometals, 2018, 31(4), 505-515.
[http://dx.doi.org/10.1007/s10534-018-0096-4] [PMID: 29623473]
[44]
Wu, J.; Chen, W.; Yin, Y.; Zheng, Z.; Zou, G. Probing the cell death signaling pathway of HepG2 cell line induced by copper-1,10-phenanthroline complex. Biometals, 2014, 27(3), 445-458.
[http://dx.doi.org/10.1007/s10534-014-9710-2] [PMID: 24638265]
[45]
Hamel, F.G.; Upward, J.L.; Siford, G.L.; Duckworth, W.C. Inhibition of proteasome activity by selected amino acids. Metabolism, 2003, 52(7), 810-814.
[http://dx.doi.org/10.1016/S0026-0495(03)00094-5] [PMID: 12870152]
[46]
Phang, C.W.; Karsani, S.A.; Sethi, G.; Abd Malek, S.N.; Flavokawain, C. Flavokawain c inhibits cell cycle and promotes apoptosis, associated with endoplasmic reticulum stress and regulation of mapks and akt signaling pathways in hct 116 human colon carcinoma cells. PLoS One, 2016, 11(2)e0148775
[http://dx.doi.org/10.1371/journal.pone.0148775] [PMID: 26859847]
[47]
Pisano, C.; Vesci, L.; Milazzo, F.M.; Guglielmi, M.B.; Foderà, R.; Barbarino, M.; D’Incalci, M.; Zucchetti, M.; Petrangolini, G.; Tortoreto, M.; Perego, P.; Zuco, V.; Orlandi, A.; Passeri, D.; Carminati, P.; Cavazza, C.; Zunino, F. Metabolic approach to the enhancement of antitumor effect of chemotherapy: A key role of acetyl-L-carnitine. Clin. Cancer Res., 2010, 16(15), 3944-3953.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0964] [PMID: 20562210]
[48]
Yilmaz, V.T.; Icsel, C.; Batur, J.; Aydinlik, S.; Sahinturk, P.; Aygun, M. Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents. Eur. J. Med. Chem., 2017, 139, 901-916.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.062] [PMID: 28881285]
[49]
Ke, N.; Wang, X.; Xu, X.; Abassi, Y.A. The xCELLigence system for real-time and label-free monitoring of cell viability. Methods Mol. Biol., 2011, 740, 33-43.
[http://dx.doi.org/10.1007/978-1-61779-108-6_6] [PMID: 21468966]
[50]
Otto, T.; Sicinski, P. Cell cycle proteins as promising targets in cancer therapy. Nat. Rev. Cancer, 2017, 17(2), 93-115.
[http://dx.doi.org/10.1038/nrc.2016.138] [PMID: 28127048]
[51]
Jin, G.; Wang, K.; Liu, Y.; Liu, X.; Zhang, X.; Zhang, H. Proteomic level changes on treatment in mcf-7/ddp breast cancer drug- resistant cells. Anticancer. Agents Med. Chem., 2020, 20(6), 687-699.
[http://dx.doi.org/10.2174/1871520620666200213102849] [PMID: 32053082]
[52]
Doan, P.; Musa, A.; Candeias, N.R.; Emmert-Streib, F.; Yli-Harja, O.; Kandhavelu, M. Alkylaminophenol induces g1/s phase cell cycle arrest in glioblastoma cells through p53 and cyclin-dependent kinase signaling pathway. Front. Pharmacol., 2019, 10(330), 330.
[http://dx.doi.org/10.3389/fphar.2019.00330] [PMID: 31001122]
[53]
Hajrezaie, M.; Paydar, M.; Moghadamtousi, S.Z.; Hassandarvish, P.; Gwaram, N.S.; Zahedifard, M.; Rouhollahi, E.; Karimian, H.; Looi, C.Y.; Ali, H.M.; Abdul Majid, N.; Abdulla, M.A. A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway. ScientificWorldJournal, 2014, 2014540463
[http://dx.doi.org/10.1155/2014/540463] [PMID: 24737979]
[54]
Hu, J.; Liao, C.; Guo, Y.; Yang, F.; Sang, W.; Zhao, J.a. Copper(II) complexes inducing apoptosis in cancer cells, and demonstrating DNA and HSA interactions. Polyhedron, 2017, 132, 28-38.
[http://dx.doi.org/10.1016/j.poly.2017.04.018]
[55]
Czabotar, P.E.; Lessene, G.; Strasser, A.; Adams, J.M. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat. Rev. Mol. Cell Biol., 2014, 15(1), 49-63.
[http://dx.doi.org/10.1038/nrm3722] [PMID: 24355989]
[56]
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]
[57]
Ichim, G.; Tait, S.W.G. A fate worse than death: Apoptosis as an oncogenic process. Nat. Rev. Cancer, 2016, 16(8), 539-548.
[http://dx.doi.org/10.1038/nrc.2016.58] [PMID: 27364482]
[58]
Cheng, M.H.; Pan, C.Y.; Chen, N.F.; Yang, S.N.; Hsieh, S.; Wen, Z.H.; Chen, W.F.; Wang, J.W.; Lu, W.H.; Kuo, H.M. Piscidin-1 induces apoptosis via mitochondrial reactive oxygen species-regulated mitochondrial dysfunction in human osteosarcoma cells. Sci. Rep., 2020, 10(1), 5045.
[http://dx.doi.org/10.1038/s41598-020-61876-5] [PMID: 32193508]
[59]
Circu, M.L.; Aw, T.Y. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med., 2010, 48(6), 749-762.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.12.022] [PMID: 20045723]
[60]
McDonnell, M.A.; Wang, D.; Khan, S.M.; Vander Heiden, M.G.; Kelekar, A. Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells. Cell Death Differ., 2003, 10(9), 1005-1015.
[http://dx.doi.org/10.1038/sj.cdd.4401271] [PMID: 12934075]
[61]
Morishima, N.; Nakanishi, K.; Takenouchi, H.; Shibata, T.; Yasuhiko, Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J. Biol. Chem., 2002, 277(37), 34287-34294.
[http://dx.doi.org/10.1074/jbc.M204973200] [PMID: 12097332]
[62]
Zhang, Q.; Liu, J.; Chen, S.; Liu, J.; Liu, L.; Liu, G.; Wang, F.; Jiang, W.; Zhang, C.; Wang, S.; Yuan, X. Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress. Apoptosis, 2016, 21(4), 432-442.
[http://dx.doi.org/10.1007/s10495-016-1217-6] [PMID: 26801321]
[63]
Vanden Berghe, T.; Linkermann, A.; Jouan-Lanhouet, S.; Walczak, H.; Vandenabeele, P. Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol., 2014, 15(2), 135-147.
[http://dx.doi.org/10.1038/nrm3737] [PMID: 24452471]
[64]
Chen, Q.; Kang, J.; Fu, C. The independence of and associations among apoptosis, autophagy, and necrosis. Signal transduction and targeted therapy, 2018, 3, 1-11.
[65]
Kandoth, C.; McLellan, M.D.; Vandin, F.; Ye, K.; Niu, B.; Lu, C.; Xie, M.; Zhang, Q.; McMichael, J.F.; Wyczalkowski, M.A.; Leiserson, M.D.M.; Miller, C.A.; Welch, J.S.; Walter, M.J.; Wendl, M.C.; Ley, T.J.; Wilson, R.K.; Raphael, B.J.; Ding, L. Mutational landscape and significance across 12 major cancer types. Nature, 2013, 502(7471), 333-339.
[http://dx.doi.org/10.1038/nature12634] [PMID: 24132290]
[66]
Porta-Pardo, E.; Kamburov, A.; Tamborero, D.; Pons, T.; Grases, D.; Valencia, A.; Lopez-Bigas, N.; Getz, G.; Godzik, A. Comparison of algorithms for the detection of cancer drivers at subgene resolution. Nat. Methods, 2017, 14(8), 782-788.
[http://dx.doi.org/10.1038/nmeth.4364] [PMID: 28714987]
[67]
Aubrey, B.J.; Kelly, G.L.; Janic, A.; Herold, M.J.; Strasser, A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ., 2018, 25(1), 104-113.
[http://dx.doi.org/10.1038/cdd.2017.169] [PMID: 29149101]
[68]
Muller, P.A.J.; Trinidad, A.G.; Timpson, P.; Morton, J.P.; Zanivan, S.; van den Berghe, P.V.E.; Nixon, C.; Karim, S.A.; Caswell, P.T.; Noll, J.E.; Coffill, C.R.; Lane, D.P.; Sansom, O.J.; Neilsen, P.M.; Norman, J.C.; Vousden, K.H. Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene, 2013, 32(10), 1252-1265.
[http://dx.doi.org/10.1038/onc.2012.148] [PMID: 22580601]
[69]
Vogiatzi, F.; Brandt, D.T.; Schneikert, J.; Fuchs, J.; Grikscheit, K.; Wanzel, M.; Pavlakis, E.; Charles, J.P.; Timofeev, O.; Nist, A.; Mernberger, M.; Kantelhardt, E.J.; Siebolts, U.; Bartel, F.; Jacob, R.; Rath, A.; Moll, R.; Grosse, R.; Stiewe, T. Mutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5. Proc. Natl. Acad. Sci. USA, 2016, 113(52), E8433-E8442.
[http://dx.doi.org/10.1073/pnas.1612711114] [PMID: 27956623]
[70]
Fiorini, C.; Cordani, M.; Padroni, C.; Blandino, G.; Di Agostino, S.; Donadelli, M. Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine. Biochim. Biophys. Acta, 2015, 1853(1), 89-100.
[http://dx.doi.org/10.1016/j.bbamcr.2014.10.003] [PMID: 25311384]
[71]
Mantovani, F.; Collavin, L.; Del Sal, G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ., 2019, 26(2), 199-212.
[http://dx.doi.org/10.1038/s41418-018-0246-9] [PMID: 30538286]
[72]
Yang, L.; Zhou, Y.; Li, Y.; Zhou, J.; Wu, Y.; Cui, Y.; Yang, G.; Hong, Y. Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett., 2015, 357(2), 520-526.
[http://dx.doi.org/10.1016/j.canlet.2014.12.003] [PMID: 25499080]
[73]
Chen, J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect. Med., 2016, 6(3)a026104
[http://dx.doi.org/10.1101/cshperspect.a026104] [PMID: 26931810]
[74]
Zhu, H-B.; Yang, K.; Xie, Y-Q.; Lin, Y-W.; Mao, Q-Q.; Xie, L-P. Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells. World J. Surg. Oncol., 2013, 11(1), 22.
[http://dx.doi.org/10.1186/1477-7819-11-22] [PMID: 23356234]
[75]
Blandino, G.; Di Agostino, S. New therapeutic strategies to treat human cancers expressing mutant p53 proteins. J. Exp. Clin. Cancer Res.,, 2018, 37(1), 30.
[http://dx.doi.org/10.1186/s13046-018-0705-7] [PMID: 29448954]

Rights & Permissions Print Cite
Article Metrics
52
1
© 2024 Bentham Science Publishers | Privacy Policy