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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Yadi Geng, Lingli Li, Ping Liu, Zhaolin Chen, Aizong Shen* and Lei Zhang *

DOI: 10.2174/1871520621666210901101510

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TMT-Based Quantitative Proteomic Analysis Identified Proteins and Signaling Pathways Involved in the Response to Xanthatin Treatment in Human HT-29 Colon Cancer Cells

Page: [887 - 896] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: Xanthatin is a plant-derived bioactive sesquiterpene lactone from the Xanthium strumarium L., and it has been used as a traditional Chinese medicine. Recently, many studies have reported that xanthatin has anticancer activity. However, a comprehensive understanding of the mechanism underlying the antitumor effects of xanthatin is still lacking.

Objective: To systematically and comprehensively identify the underlying mechanisms of xanthatin on cancer cells, quantitative proteomic techniques were performed.

Methods: Xanthatin induced HT-29 colon cancer cells death was detected by lactate dehydrogenase (LDH) release cell death assay. Differentially abundant proteins in two groups (xanthatin treatment groups and control groups) of human HT-29 colon cancer cells were identified using tandem mass tag (TMT) quantitative proteomic techniques. All the significant differentially abundant proteins were generally characterized by performing hierarchical clustering, Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We chose Western blot analysis to validate the candidate proteins in the proteomics results.

Results: A total of 5637 proteins were identified, of which 397 significantly differentially abundant proteins in the groups were quantified. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we found that p53-related signaling played an important role in xanthatin-treated HT-29 colon cancer cells. p53- upregulated modulator of apoptosis (Puma), Sestrin-2 and p14ARF, which were selected from among p53-related signaling proteins, were further validated, and the results were consistent with the tandem mass tag quantitative proteomic results.

Conclusion: We first investigated the molecular mechanism underlying the effects of xanthatin treatment on HT-29 colon cancer cells using tandem mass tag quantitative proteomic methods and provided a global comprehensive understanding of the antitumor effects of xanthatin. However, it is necessary to further confirm the function of the differentially abundant proteins and the potentially associated signaling pathways.

Keywords: Xanthatin, TMT, LC-MS-MS, proteomic, mechanism, HT-29 colon cancer cells.

Graphical Abstract

[1]
Fan, W.; Fan, L.; Peng, C.; Zhang, Q.; Wang, L.; Li, L.; Wang, J.; Zhang, D.; Peng, W.; Wu, C. Traditional uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A review. Molecules, 2019, 24(2), E359.
[http://dx.doi.org/10.3390/molecules24020359] [PMID: 30669496]
[2]
Liu, M.; Xiao, C.Q.; Sun, M.W.; Tan, M.J.; Hu, L.H.; Yu, Q. Xanthatin inhibits STAT3 and NF-κB signalling by covalently binding to JAK and IKK kinases. J. Cell. Mol. Med., 2019, 23(6), 4301-4312.
[http://dx.doi.org/10.1111/jcmm.14322] [PMID: 30993883]
[3]
Hossen, M.J.; Cho, J.Y.; Kim, D. PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities. J. Ethnopharmacol., 2016, 190, 251-260.
[http://dx.doi.org/10.1016/j.jep.2016.06.019] [PMID: 27286918]
[4]
Lin, B.; Zhao, Y.; Han, P.; Yue, W.; Ma, X.Q.; Rahman, K.; Zheng, C.J.; Qin, L.P.; Han, T. Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund׳s adjuvant induced arthritis in rats. J. Ethnopharmacol., 2014, 155(1), 248-255.
[http://dx.doi.org/10.1016/j.jep.2014.05.023] [PMID: 24862493]
[5]
Ma, Y.Y.; Di, Z.M.; Cao, Q.; Xu, W.S.; Bi, S.X.; Yu, J.S.; Shen, Y.J.; Yu, Y.Q.; Shen, Y.X.; Feng, L.J. Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway. Acta Pharmacol. Sin., 2020, 41(3), 404-414.
[http://dx.doi.org/10.1038/s41401-019-0318-5] [PMID: 31700088]
[6]
Shi, T.L.; Zhang, L.; Cheng, Q.Y.; Yu, J.S.; Liu, J.; Shen, Y.J.; Feng, X.J.; Shen, Y.X. Xanthatin induces apoptosis by activating endoplasmic reticulum stress in hepatoma cells. Eur. J. Pharmacol., 2019, 843, 1-11.
[http://dx.doi.org/10.1016/j.ejphar.2018.10.041] [PMID: 30389633]
[7]
Yu, Y.; Yu, J.; Pei, C.G.; Li, Y.Y.; Tu, P.; Gao, G.P.; Shao, Y. Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells. Int. J. Clin. Exp. Pathol., 2015, 8(9), 10355-10364.
[PMID: 26617743]
[8]
Zhang, L.; Tao, L.; Ruan, J.; Li, W.; Wu, Y.; Yan, L.; Zhang, F.; Fan, F.; Zheng, S.; Wang, A.; Lu, Y. Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells. Planta Med., 2012, 78(9), 890-895.
[http://dx.doi.org/10.1055/s-0031-1298481] [PMID: 22532019]
[9]
Zhang, L.; Ruan, J.; Yan, L.; Li, W.; Wu, Y.; Tao, L.; Zhang, F.; Zheng, S.; Wang, A.; Lu, Y. Xanthatin induces cell cycle arrest at G2/M checkpoint and apoptosis via disrupting NF-κB pathway in A549 non-small-cell lung cancer cells. Molecules, 2012, 17(4), 3736-3750.
[http://dx.doi.org/10.3390/molecules17043736] [PMID: 22450683]
[10]
Vermeulen, K.; Van Bockstaele, D.R.; Berneman, Z.N. Apoptosis: mechanisms and relevance in cancer. Ann. Hematol., 2005, 84(10), 627-639.
[http://dx.doi.org/10.1007/s00277-005-1065-x] [PMID: 16041532]
[11]
Doonan, F.; Cotter, T.G. Morphological assessment of apoptosis. Methods, 2008, 44(3), 200-204.
[http://dx.doi.org/10.1016/j.ymeth.2007.11.006] [PMID: 18314050]
[12]
Carneiro, B.A.; El-Deiry, W.S. Targeting apoptosis in cancer therapy. Nat. Rev. Clin. Oncol., 2020, 17(7), 395-417.
[http://dx.doi.org/10.1038/s41571-020-0341-y] [PMID: 32203277]
[13]
Lu, W.; Jia, G.; Meng, X.; Zhao, C.; Zhang, L.; Ren, Y.; Pan, H.; Ni, Y. Beta-catenin mediates the apoptosis induction effect of celastrol in HT29 cells. Life Sci., 2012, 91(7-8), 279-283.
[http://dx.doi.org/10.1016/j.lfs.2012.07.032] [PMID: 22877649]
[14]
Bai, X.; Wang, Y.; Hu, B.; Cao, Q.; Xing, M.; Song, S.; Ji, A. Fucoidan induces apoptosis of HT-29 cells via the activation of DR4 and mitochondrial pathway. Mar. Drugs, 2020, 18(4), E220.
[http://dx.doi.org/10.3390/md18040220] [PMID: 32326052]
[15]
Sun, P.; Sun, D.; Wang, X. Effects of Scutellaria barbata polysaccharide on the proliferation, apoptosis and EMT of human colon cancer HT29 Cells. Carbohydr. Polym., 2017, 167, 90-96.
[http://dx.doi.org/10.1016/j.carbpol.2017.03.022] [PMID: 28433181]
[16]
Geng, Y.D.; Zhang, L.; Wang, G.Y.; Feng, X.J.; Chen, Z.L.; Jiang, L.; Shen, A.Z. Xanthatin mediates G2/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells. Nat. Prod. Res., 2020, 34(18), 2616-2620.
[http://dx.doi.org/10.1080/14786419.2018.1544976] [PMID: 30587055]
[17]
Matthiesen, R.; Azevedo, L.; Amorim, A.; Carvalho, A.S. Discussion on common data analysis strategies used in MS-based proteomics. Proteomics, 2011, 11(4), 604-619.
[http://dx.doi.org/10.1002/pmic.201000404] [PMID: 21241018]
[18]
Zhang, K.; Tian, S.; Fan, E. Protein lysine acetylation analysis: current MS-based proteomic technologies. Analyst (Lond.), 2013, 138(6), 1628-1636.
[http://dx.doi.org/10.1039/c3an36837h] [PMID: 23361263]
[19]
Li, L.H.; Huang, Q.M.; Barbero, M.; Liu, L.; Nguyen, T.T.; Beretta-Piccoli, M.; Xu, A.L.; Ji, L.J. Quantitative proteomics analysis to identify biomarkers of chronic myofascial pain and therapeutic targets of dry needling in a rat model of myofascial trigger points. J. Pain Res., 2019, 12, 283-298.
[http://dx.doi.org/10.2147/JPR.S185916] [PMID: 30662282]
[20]
McAlister, G.C.; Huttlin, E.L.; Haas, W.; Ting, L.; Jedrychowski, M.P.; Rogers, J.C.; Kuhn, K.; Pike, I.; Grothe, R.A.; Blethrow, J.D.; Gygi, S.P. Increasing the multiplexing capacity of TMTs using reporter ion isotopologues with isobaric masses. Anal. Chem., 2012, 84(17), 7469-7478.
[http://dx.doi.org/10.1021/ac301572t] [PMID: 22880955]
[21]
Thompson, A.; Schäfer, J.; Kuhn, K.; Kienle, S.; Schwarz, J.; Schmidt, G.; Neumann, T.; Johnstone, R.; Mohammed, A.K.; Hamon, C. Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal. Chem., 2003, 75(8), 1895-1904.
[http://dx.doi.org/10.1021/ac0262560] [PMID: 12713048]
[22]
La, Y.; Tang, J.; Guo, X.; Zhang, L.; Gan, S.; Zhang, X.; Zhang, J.; Hu, W.; Chu, M. Proteomic analysis of sheep uterus reveals its role in prolificacy. J. Proteomics, 2020, 210, 103526.
[http://dx.doi.org/10.1016/j.jprot.2019.103526] [PMID: 31605788]
[23]
Hou, C.; Guo, D.; Yu, X.; Wang, S.; Liu, T. TMT-based proteomics analysis of the anti-hepatocellular carcinoma effect of combined dihydroartemisinin and sorafenib. Biomed. Pharmacother., 2020, 126, 109862.
[http://dx.doi.org/10.1016/j.biopha.2020.109862] [PMID: 32120157]
[24]
Zheng, W.; Xu, S. Analysis of Differential Expression Proteins of Paclitaxel-Treated Lung Adenocarcinoma Cell A549 Using Tandem Mass Tag-Based Quantitative Proteomics. OncoTargets Ther., 2020, 13, 10297-10313.
[http://dx.doi.org/10.2147/OTT.S259895] [PMID: 33116610]
[25]
Nibret, E.; Youns, M.; Krauth-Siegel, R.L.; Wink, M. Biological activities of xanthatin from Xanthium strumarium leaves. Phytother. Res., 2011, 25(12), 1883-1890.
[http://dx.doi.org/10.1002/ptr.3651] [PMID: 21953905]
[26]
Lavault, M.; Landreau, A.; Larcher, G.; Bouchara, J.P.; Pagniez, F.; Le Pape, P.; Richomme, P. Antileishmanial and antifungal activities of xanthanolides isolated from Xanthium macrocarpum. Fitoterapia, 2005, 76(3-4), 363-366.
[http://dx.doi.org/10.1016/j.fitote.2005.03.019] [PMID: 15890467]
[27]
Domokos, E.; Kursinszki, L.; Kelemen, H.; Varga, E. Phytopharmacological review of bathurst burr (Xanthium spinosum L.). Acta Pharm. Hung., 2016, 86(1), 35. [Phytopharmacological review of bathurst burr (Xanthium spinosum L.)].
[PMID: 27295875]
[28]
Sato, Y.; Oketani, H.; Yamada, T.; Singyouchi, K.; Ohtsubo, T.; Kihara, M.; Shibata, H.; Higuti, T. A xanthanolide with potent antibacterial activity against methicillin-resistant Staphylococcus aureus. J. Pharm. Pharmacol., 1997, 49(10), 1042-1044.
[http://dx.doi.org/10.1111/j.2042-7158.1997.tb06038.x] [PMID: 9364417]
[29]
Shen, M.; Zhou, X.Z.; Ye, L.; Yuan, Q.; Shi, C.; Zhu, P.W.; Jiang, N.; Ma, M.Y.; Yang, Q.C.; Shao, Y. Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2 mediated STAT3/PI3K/Akt signaling pathway. Int. J. Mol. Med., 2018, 42(2), 769-778.
[http://dx.doi.org/10.3892/ijmm.2018.3646] [PMID: 29717775]
[30]
Romero, M.; Zanuy, M.; Rosell, E.; Cascante, M.; Piulats, J.; Font-Bardia, M.; Balzarini, J.; De Clerq, E.; Pujol, M.D. Optimization of xanthatin extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties. Eur. J. Med. Chem., 2015, 90, 491-496.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.060] [PMID: 25481815]
[31]
Tao, L.; Sheng, X.; Zhang, L.; Li, W.; Wei, Z.; Zhu, P.; Zhang, F.; Wang, A.; Woodgett, J.R.; Lu, Y. Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin. Biochem. Pharmacol., 2016, 115, 18-27.
[http://dx.doi.org/10.1016/j.bcp.2016.06.009] [PMID: 27321043]
[32]
Tao, L.; Fan, F.; Liu, Y.; Li, W.; Zhang, L.; Ruan, J.; Shen, C.; Sheng, X.; Zhu, Z.; Wang, A.; Chen, W.; Huang, S.; Lu, Y. Concerted suppression of STAT3 and GSK3β is involved in growth inhibition of non-small cell lung cancer by Xanthatin. PLoS One, 2013, 8(11), e81945.
[http://dx.doi.org/10.1371/journal.pone.0081945] [PMID: 24312384]
[33]
Zhang, J.; Yang, S.; Guan, H.; Zhou, J.; Gao, Y. Xanthatin synergizes with cisplatin to suppress homologous recombination through JAK2/STAT4/BARD1 axis in human NSCLC cells. J. Cell. Mol. Med., 2021, 25(3), 1688-1699.
[http://dx.doi.org/10.1111/jcmm.16271] [PMID: 33439503]
[34]
Liu, R.; Shi, D.; Zhang, J.; Li, X.; Han, X.; Yao, X.; Fang, J. Xanthatin promotes apoptosis via inhibiting thioredoxin reductase and eliciting oxidative stress. Mol. Pharm., 2018, 15(8), 3285-3296.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00338] [PMID: 29939757]
[35]
Ohlendieck, K. Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques. Skelet. Muscle, 2011, 1(1), 6.
[http://dx.doi.org/10.1186/2044-5040-1-6] [PMID: 21798084]
[36]
Hafner, A.; Bulyk, M.L.; Jambhekar, A.; Lahav, G. The multiple mechanisms that regulate p53 activity and cell fate. Nat. Rev. Mol. Cell Biol., 2019, 20(4), 199-210.
[http://dx.doi.org/10.1038/s41580-019-0110-x] [PMID: 30824861]
[37]
Goldar, S.; Khaniani, M.S.; Derakhshan, S.M.; Baradaran, B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac. J. Cancer Prev., 2015, 16(6), 2129-2144.
[http://dx.doi.org/10.7314/APJCP.2015.16.6.2129] [PMID: 25824729]
[38]
Wang, Y.; Tian, J.; Huang, C.; Ma, J.; Hu, G.; Chen, Y.; Wang, T.; Cai, R.; Zuo, Y.; Tan, H.; Fan, Q.; Dong, B.; Xue, W.; Yi, J.; Chen, G.; Tu, J.; Cheng, J. P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint. Cell Discov., 2020, 6, 21.
[http://dx.doi.org/10.1038/s41421-020-0154-2]
[39]
Won, Y.S.; Seo, K.I.; Sanggenol, L. Sanggenol L induces apoptosis and cell cycle arrest via activation of p53 and suppression of PI3K/Akt/mTOR signaling in human prostate cancer cells. Nutrients, 2020, 12(2), E488.
[http://dx.doi.org/10.3390/nu12020488] [PMID: 32075054]
[40]
Ryu, H.; Nam, K.Y.; Kim, J.S.; Hwang, S.G.; Song, J.Y.; Ahn, J. The small molecule AU14022 promotes colorectal cancer cell death via p53-mediated G2/M-phase arrest and mitochondria-mediated apoptosis. J. Cell. Physiol., 2018, 233(6), 4666-4676.
[http://dx.doi.org/10.1002/jcp.26234] [PMID: 29030986]
[41]
Taylor, W.R.; Stark, G.R. Regulation of the G2/M transition by p53. Oncogene, 2001, 20(15), 1803-1815.
[http://dx.doi.org/10.1038/sj.onc.1204252] [PMID: 11313928]
[42]
Pagani, F.D.; DiMicco, J.A.; Hamilton, B.L.; Souza, J.D.; Schmidt, B.; Gillis, R.A. Stress-induced changes in the function of the parasympathetic nervous system are mimicked by blocking GABA in the CNS of the cat. Neuropharmacology, 1987, 26(2-3), 155-160.
[http://dx.doi.org/10.1016/0028-3908(87)90203-6] [PMID: 3035411]
[43]
Lu, Y.F.; Xu, X.P.; Lu, X.P.; Zhu, Q.; Liu, G.; Bao, Y.T.; Wen, H.; Li, Y.L.; Gu, W.; Zhu, W.G. SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle. Oncogene, 2020, 39(24), 4650-4665.
[http://dx.doi.org/10.1038/s41388-020-1305-5] [PMID: 32404984]
[44]
Zamzami, N.; Kroemer, G. p53 in apoptosis control: an introduction. Biochem. Biophys. Res. Commun., 2005, 331(3), 685-687.
[http://dx.doi.org/10.1016/j.bbrc.2005.04.013] [PMID: 15865922]
[45]
Lin, R.W.; Ho, C.J.; Chen, H.W.; Pao, Y.H.; Chen, L.E.; Yang, M.C.; Huang, S.B.; Wang, S.; Chen, C.H.; Wang, C. P53 enhances apoptosis induced by doxorubicin only under conditions of severe DNA damage. Cell Cycle, 2018, 17(17), 2175-2186.
[http://dx.doi.org/10.1080/15384101.2018.1520565] [PMID: 30198376]
[46]
Rufini, A.; Tucci, P.; Celardo, I.; Melino, G. Senescence and aging: the critical roles of p53. Oncogene, 2013, 32(43), 5129-5143.
[http://dx.doi.org/10.1038/onc.2012.640] [PMID: 23416979]
[47]
Beck, J.; Turnquist, C.; Horikawa, I.; Harris, C. Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms. Carcinogenesis, 2020, 41(8), 1017-1029.
[http://dx.doi.org/10.1093/carcin/bgaa071] [PMID: 32619002]
[48]
Kim, Y.Y.; Um, J.H.; Shin, D.J.; Jeong, D.J.; Hong, Y.B.; Yun, J. p53-mediated regulation of mitochondrial dynamics plays a pivotal role in the senescence of various normal cells as well as cancer cells. FASEB J., 2021, 35(2), e21319.
[http://dx.doi.org/10.1096/fj.202002007R] [PMID: 33433933]
[49]
Hong, B.; van den Heuvel, A.P.; Prabhu, V.V.; Zhang, S.; El-Deiry, W.S. Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities. Curr. Drug Targets, 2014, 15(1), 80-89.
[http://dx.doi.org/10.2174/1389450114666140106101412] [PMID: 24387333]
[50]
Tao, L.; Cao, Y.; Wei, Z.; Jia, Q.; Yu, S.; Zhong, J.; Wang, A.; Woodgett, J.R.; Lu, Y. Xanthatin triggers Chk1-mediated DNA damage response and destabilizes Cdc25C via lysosomal degradation in lung cancer cells. Toxicol. Appl. Pharmacol., 2017, 337, 85-94.
[http://dx.doi.org/10.1016/j.taap.2017.10.015] [PMID: 29074359]
[51]
Cai, W.; Li, Q.; Yang, Z.; Miao, X.; Wen, Y.; Huang, S.; Ouyang, J. Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance. Clin. Transl. Oncol., 2013, 15(10), 818-824.
[http://dx.doi.org/10.1007/s12094-013-1010-8] [PMID: 23475628]
[52]
Du, Q.H.; Zhang, K.J.; Jiao, X.L.; Zhao, J.; Zhang, M.; Yan, B.M.; Xu, Y.B. Prognostic significance of PUMA in pancreatic ductal adenocarcinoma. J. Int. Med. Res., 2012, 40(6), 2066-2072.
[http://dx.doi.org/10.1177/030006051204000603] [PMID: 23321162]
[53]
Kim, M.R.; Jeong, E.G.; Chae, B.; Lee, J.W.; Soung, Y.H.; Nam, S.W.; Lee, J.Y.; Yoo, N.J.; Lee, S.H. Pro-apoptotic PUMA and anti-apoptotic phospho-BAD are highly expressed in colorectal carcinomas. Dig. Dis. Sci., 2007, 52(10), 2751-2756.
[http://dx.doi.org/10.1007/s10620-007-9799-z] [PMID: 17393317]
[54]
Yee, K.S.; Vousden, K.H. Contribution of membrane localization to the apoptotic activity of PUMA. Apoptosis, 2008, 13(1), 87-95.
[http://dx.doi.org/10.1007/s10495-007-0140-2] [PMID: 17968660]
[55]
Han, C.W.; Lee, H.N.; Jeong, M.S.; Park, S.Y.; Jang, S.B. Structural basis of the p53 DNA binding domain and PUMA complex. Biochem. Biophys. Res. Commun., 2021, 548, 39-46.
[http://dx.doi.org/10.1016/j.bbrc.2021.02.049] [PMID: 33631672]
[56]
Yu, J.; Wang, Z.; Kinzler, K.W.; Vogelstein, B.; Zhang, L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc. Natl. Acad. Sci. USA, 2003, 100(4), 1931-1936.
[http://dx.doi.org/10.1073/pnas.2627984100] [PMID: 12574499]
[57]
Hikisz, P.; Kiliańska, Z.M. PUMA, a critical mediator of cell death--one decade on from its discovery. Cell. Mol. Biol. Lett., 2012, 17(4), 646-669.
[http://dx.doi.org/10.2478/s11658-012-0032-5] [PMID: 23001513]
[58]
Zhang, L.N.; Li, J.Y.; Xu, W. A review of the role of Puma, Noxa and Bim in the tumorigenesis, therapy and drug resistance of chronic lymphocytic leukemia. Cancer Gene Ther., 2013, 20(1), 1-7.
[http://dx.doi.org/10.1038/cgt.2012.84] [PMID: 23175245]
[59]
Qiu, W.; Wu, B.; Wang, X.; Buchanan, M.E.; Regueiro, M.D.; Hartman, D.J.; Schoen, R.E.; Yu, J.; Zhang, L. PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice. J. Clin. Invest., 2011, 121(5), 1722-1732.
[http://dx.doi.org/10.1172/JCI42917] [PMID: 21490394]
[60]
Fan, S.; Qi, M.; Yu, Y.; Li, L.; Yao, G.; Tashiro, S.; Onodera, S.; Ikejima, T. P53 activation plays a crucial role in silibinin induced ROS generation via PUMA and JNK. Free Radic. Res., 2012, 46(3), 310-319.
[http://dx.doi.org/10.3109/10715762.2012.655244] [PMID: 22283740]
[61]
Liu, Z.; Lu, H.; Shi, H.; Du, Y.; Yu, J.; Gu, S.; Chen, X.; Liu, K.J.; Hu, C.A. PUMA overexpression induces reactive oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells. Cancer Res., 2005, 65(5), 1647-1654.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1754] [PMID: 15753358]
[62]
Liu, B.; Yuan, B.; Zhang, L.; Mu, W.; Wang, C. ROS/p38/p53/Puma signaling pathway is involved in emodin-induced apoptosis of human colorectal cancer cells. Int. J. Clin. Exp. Med., 2015, 8(9), 15413-15422.
[PMID: 26629030]
[63]
Tan, X.; Zhang, Z.; Liu, P.; Yao, H.; Shen, L.; Tong, J.S. Inhibition of EZH2 enhances the therapeutic effect of 5-FU via PUMA upregulation in colorectal cancer. Cell Death Dis., 2020, 11(12), 1061.
[http://dx.doi.org/10.1038/s41419-020-03266-3] [PMID: 33311453]
[64]
Zhang, X.Y.; Wu, X.Q.; Deng, R.; Sun, T.; Feng, G.K.; Zhu, X.F. Upregulation of sestrin 2 expression via JNK pathway activation contributes to autophagy induction in cancer cells. Cell. Signal., 2013, 25(1), 150-158.
[http://dx.doi.org/10.1016/j.cellsig.2012.09.004] [PMID: 22982090]
[65]
Budanov, A.V.; Shoshani, T.; Faerman, A.; Zelin, E.; Kamer, I.; Kalinski, H.; Gorodin, S.; Fishman, A.; Chajut, A.; Einat, P.; Skaliter, R.; Gudkov, A.V.; Chumakov, P.M.; Feinstein, E. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene, 2002, 21(39), 6017-6031.
[http://dx.doi.org/10.1038/sj.onc.1205877] [PMID: 12203114]
[66]
Jayaraj, P.; Sen, S.; Rangarajan, S.; Ray, N.; Vasu, K.; Singh, V.K.; Phartyal, R.; Yadav, S.; Verma, A. Immunohistochemical evaluation of stress-responsive protein sestrin2 and its correlation with p53 mutational status in eyelid sebaceous gland carcinoma. Br. J. Ophthalmol., 2018, 102(6), 848-854.
[http://dx.doi.org/10.1136/bjophthalmol-2017-311283] [PMID: 29478030]
[67]
Jin, H.R.; Du, C.H.; Wang, C.Z.; Yuan, C.S.; Du, W. Ginseng metabolite Protopanaxadiol induces Sestrin2 expression and AMPK activation through GCN2 and PERK. Cell Death Dis., 2019, 10(4), 311.
[http://dx.doi.org/10.1038/s41419-019-1548-7] [PMID: 30952841]
[68]
Wang, N.; Pan, W.; Zhu, M.; Zhang, M.; Hao, X.; Liang, G.; Feng, Y. Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells. Br. J. Pharmacol., 2011, 164(2b), 731-742.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01349.x] [PMID: 21418191]
[69]
Kim, G.T.; Lee, S.H.; Kim, J.I.; Kim, Y.M. Quercetin regulates the sestrin 2-AMPK-p38 MAPK signaling pathway and induces apoptosis by increasing the generation of intracellular ROS in a p53-independent manner. Int. J. Mol. Med., 2014, 33(4), 863-869.
[http://dx.doi.org/10.3892/ijmm.2014.1658] [PMID: 24535669]
[70]
Wolfson, R.L.; Chantranupong, L.; Saxton, R.A.; Shen, K.; Scaria, S.M.; Cantor, J.R.; Sabatini, D.M. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science, 2016, 351(6268), 43-48.
[http://dx.doi.org/10.1126/science.aab2674] [PMID: 26449471]
[71]
Saxton, R.A.; Knockenhauer, K.E.; Wolfson, R.L.; Chantranupong, L.; Pacold, M.E.; Wang, T.; Schwartz, T.U.; Sabatini, D.M. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science, 2016, 351(6268), 53-58.
[http://dx.doi.org/10.1126/science.aad2087] [PMID: 26586190]
[72]
Brüning, A.; Rahmeh, M.; Friese, K. Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation. Mol. Oncol., 2013, 7(6), 1012-1018.
[http://dx.doi.org/10.1016/j.molonc.2013.07.010] [PMID: 23916134]
[73]
Won, D.H.; Chung, S.H.; Shin, J.A.; Hong, K.O.; Yang, I.H.; Yun, J.W.; Cho, S.D. Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines. J. Clin. Biochem. Nutr., 2019, 64(2), 97-105.
[http://dx.doi.org/10.3164/jcbn.18-63] [PMID: 30936621]
[74]
Luchinat, E.; Chiarella, S.; Franceschini, M.; Di Matteo, A.; Brunori, M.; Banci, L.; Federici, L. Identification of a novel nucleophosmin-interaction motif in the tumor suppressor p14arf. FEBS J., 2018, 285(5), 832-847.
[http://dx.doi.org/10.1111/febs.14373] [PMID: 29283500]
[75]
Wang, J.; Ding, S.; Duan, Z.; Xie, Q.; Zhang, T.; Zhang, X.; Wang, Y.; Chen, X.; Zhuang, H.; Lu, F. Role of p14ARF-HDM2-p53 axis in SOX6-mediated tumor suppression. Oncogene, 2016, 35(13), 1692-1702.
[http://dx.doi.org/10.1038/onc.2015.234] [PMID: 26119940]
[76]
Sekaric, P.; Shamanin, V.A.; Luo, J.; Androphy, E.J. hAda3 regulates p14ARF-induced p53 acetylation and senescence. Oncogene, 2007, 26(43), 6261-6268.
[http://dx.doi.org/10.1038/sj.onc.1210462] [PMID: 17452980]
[77]
Ko, A.; Han, S.Y.; Choi, C.H.; Cho, H.; Lee, M.S.; Kim, S.Y.; Song, J.S.; Hong, K.M.; Lee, H.W.; Hewitt, S.M.; Chung, J.Y.; Song, J. Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF. Cell Death Differ., 2018, 25(6), 1050-1062.
[http://dx.doi.org/10.1038/s41418-018-0072-0] [PMID: 29472714]