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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

Synergism Effect of Dendrobine on Cisplatin in Treatment of H1299 by Modulating the Balance of Treg/Th17

Author(s): Yang Luo, Gaohua Liu and Peifeng Hou*

Volume 23, Issue 1, 2023

Published on: 26 August, 2022

Page: [105 - 112] Pages: 8

DOI: 10.2174/1871520622666220520093837

Price: $65

Abstract

Background: Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancers. Cisplatin is a broad-spectrum anti-cancer drug and is often used in combination with other drugs. Research suggests that dendrobine, a pyrrolizidine derivative alkaloid, exhibits antitumor activity in various cancers. This study explores the effect of dendrobine combined with cisplatin on NSCLC and its underlying molecular mechanism.

Methods: The effects of dendrobine combined with cisplatin on tumor progression were evaluated by xenograft model (in vivo) and clonogenic survival assay (in vitro) using H1299 cell line. Annexin V staining was used for detecting apoptotic cells. The population of T cells, B cells and other subpopulations in the peripheral blood was determined by flow cytometry.

Results: Dendrobine combined with cisplatin prolonged the survival of mice implanted with H1299 cells and reduced tumor volume compared with single drug application. However, dendrobine exhibited no effect on H1299 cells in clonal survival assays with or without cisplatin treatment and did not promote cisplatin-induced apoptosis in vitro.

Importantly, dendrobine suppressed the regulatory T cells (Treg cells) and enhanced the T helper 17 cells (Th17 cells). Treatment of dendrobine significantly reduced Foxp3, and increased the level of IL-17 in serum.

Conclusion: Dendrobine displayed a synergistic effect with cisplatin to exert anti-tumor effect in vivo, which might be achieved by modulating the balance of Treg/Th17 cells rather than regulating cell apoptosis.

Keywords: Synergistic effect, dendrobine, cisplatin, non-small cell lung cancer, H1299 cell line, Treg/Th17 cells.

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[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]
Osmani, L.; Askin, F.; Gabrielson, E.; Li, Q.K. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin. Cancer Biol., 2018, 52(Pt 1), 103-109.
[http://dx.doi.org/10.1016/j.semcancer.2017.11.019] [PMID: 29183778]
[3]
Hanna, N.; Johnson, D.; Temin, S.; Baker, S., Jr; Brahmer, J.; Ellis, P.M.; Giaccone, G.; Hesketh, P.J.; Jaiyesimi, I.; Leighl, N.B.; Riely, G.J.; Schiller, J.H.; Schneider, B.J.; Smith, T.J.; Tashbar, J.; Biermann, W.A.; Masters, G. Systemic therapy for stage iv non-small-cell lung cancer: American society of clinical oncology clinical practice guideline update. J. Clin. Oncol., 2017, 35(30), 3484-3515.
[http://dx.doi.org/10.1200/JCO.2017.74.6065] [PMID: 28806116]
[4]
Planchard, D.; Popat, S.; Kerr, K.; Novello, S.; Smit, E.F.; Faivre-Finn, C.; Mok, T.S.; Reck, M.; Van Schil, P.E.; Hellmann, M.D.; Peters, S.; Committee, E.G. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2018, 29(Suppl. 4), iv192-iv237.
[http://dx.doi.org/10.1093/annonc/mdy275]
[5]
Trump, D.L.; Grem, J.L.; Tutsch, K.D.; Willson, J.K.; Simon, K.J.; Alberti, D.; Storer, B.; Tormey, D.C. Platinum analogue combination chemotherapy: Cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. J. Clin. Oncol., 1987, 5(8), 1281-1289.
[http://dx.doi.org/10.1200/JCO.1987.5.8.1281] [PMID: 3040920]
[6]
Ho, G.Y.; Woodward, N.; Coward, J.I. Cisplatin versus carboplatin: Comparative review of therapeutic management in solid malignancies. Crit. Rev. Oncol. Hematol., 2016, 102, 37-46.
[http://dx.doi.org/10.1016/j.critrevonc.2016.03.014] [PMID: 27105947]
[7]
de Castro, J.; Tagliaferri, P.; de Lima, V.C.C.; Ng, S.; Thomas, M.; Arunachalam, A.; Cao, X.; Kothari, S.; Burke, T.; Myeong, H.; Grattan, A.; Lee, D.H. Systemic therapy treatment patterns in patients with advanced non-small cell lung cancer (NSCLC): PIvOTAL study. Eur. J. Cancer Care (Engl.), 2017, 26(6), e12734.
[http://dx.doi.org/10.1111/ecc.12734] [PMID: 28748556]
[8]
Xu, W.T.; Shen, G.N.; Li, T.Z.; Zhang, Y.; Zhang, T.; Xue, H.; Zuo, W.B.; Li, Y.N.; Zhang, D.J.; Jin, C.H. Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells via the ROS regulated MAPK, STAT3 and NF κB signaling pathways. Int. J. Oncol., 2020, 57(2), 550-561.
[http://dx.doi.org/10.3892/ijo.2020.5079] [PMID: 32626938]
[9]
Demkow, U.; Stelmaszczyk-Emmel, A. Cardiotoxicity of cisplatin-based chemotherapy in advanced non-small cell lung cancer patients. Respir. Physiol. Neurobiol., 2013, 187(1), 64-67.
[http://dx.doi.org/10.1016/j.resp.2013.03.013] [PMID: 23548823]
[10]
Ma, G.F.; Zhang, R.F.; Ying, K.J.; Wang, D. Effect evaluation of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer patients using microarray data. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(4), 578-585.
[PMID: 25753874]
[11]
Roth, A.; Maibach, R.; Martinelli, G.; Fazio, N.; Aapro, M.; Pagani, O.; Morant, R.; Borner, M.; Herrmann, R.; Honegger, H.J.A.o.o. Docetaxel (Taxotere®)-cisplatin (TC): An effective drug combination in gastric carcinoma. Ann. Oncol., 2000, 11(3), 301-306.
[12]
Block, K.I.; Gyllenhaal, C.; Lowe, L.; Amedei, A.; Amin, A.R.M.R.; Amin, A.; Aquilano, K.; Arbiser, J.; Arreola, A.; Arzumanyan, A.; Ashraf, S.S.; Azmi, A.S.; Benencia, F.; Bhakta, D.; Bilsland, A.; Bishayee, A.; Blain, S.W.; Block, P.B.; Boosani, C.S.; Carey, T.E.; Carnero, A.; Carotenuto, M.; Casey, S.C.; Chakrabarti, M.; Chaturvedi, R.; Chen, G.Z.; Chen, H.; Chen, S.; Chen, Y.C.; Choi, B.K.; Ciriolo, M.R.; Coley, H.M.; Collins, A.R.; Connell, M.; Crawford, S.; Curran, C.S.; Dabrosin, C.; Damia, G.; Dasgupta, S.; DeBerardinis, R.J.; Decker, W.K.; Dhawan, P.; Diehl, A.M.E.; Dong, J.T.; Dou, Q.P.; Drew, J.E.; Elkord, E.; El-Rayes, B.; Feitelson, M.A.; Felsher, D.W.; Ferguson, L.R.; Fimognari, C.; Firestone, G.L.; Frezza, C.; Fujii, H.; Fuster, M.M.; Generali, D.; Georgakilas, A.G.; Gieseler, F.; Gilbertson, M.; Green, M.F.; Grue, B.; Guha, G.; Halicka, D.; Helferich, W.G.; Heneberg, P.; Hentosh, P.; Hirschey, M.D.; Hofseth, L.J.; Holcombe, R.F.; Honoki, K.; Hsu, H.Y.; Huang, G.S.; Jensen, L.D.; Jiang, W.G.; Jones, L.W.; Karpowicz, P.A.; Keith, W.N.; Kerkar, S.P.; Khan, G.N.; Khatami, M.; Ko, Y.H.; Kucuk, O.; Kulathinal, R.J.; Kumar, N.B.; Kwon, B.S.; Le, A.; Lea, M.A.; Lee, H.Y.; Lichtor, T.; Lin, L.T.; Locasale, J.W.; Lokeshwar, B.L.; Longo, V.D.; Lyssiotis, C.A.; MacKenzie, K.L.; Malhotra, M.; Marino, M.; Martinez-Chantar, M.L.; Matheu, A.; Maxwell, C.; McDonnell, E.; Meeker, A.K.; Mehrmohamadi, M.; Mehta, K.; Michelotti, G.A.; Mohammad, R.M.; Mohammed, S.I.; Morre, D.J.; Muralidhar, V.; Muqbil, I.; Murphy, M.P.; Nagaraju, G.P.; Nahta, R.; Niccolai, E.; Nowsheen, S.; Panis, C.; Pantano, F.; Parslow, V.R.; Pawelec, G.; Pedersen, P.L.; Poore, B.; Poudyal, D.; Prakash, S.; Prince, M.; Raffaghello, L.; Rathmell, J.C.; Rathmell, W.K.; Ray, S.K.; Reichrath, J.; Rezazadeh, S.; Ribatti, D.; Ricciardiello, L.; Robey, R.B.; Rodier, F.; Rupasinghe, H.P.V.; Russo, G.L.; Ryan, E.P.; Samadi, A.K.; Sanchez-Garcia, I.; Sanders, A.J.; Santini, D.; Sarkar, M.; Sasada, T.; Saxena, N.K.; Shackelford, R.E.; Shantha Kumara, H.M.C.; Sharma, D.; Shin, D.M.; Sidransky, D.; Siegelin, M.D.; Signori, E.; Singh, N.; Sivanand, S.; Sliva, D.; Smythe, C.; Spagnuolo, C.; Stafforini, D.M.; Stagg, J.; Subbarayan, P.R.; Sundin, T.; Talib, W.H.; Thompson, S.K.; Tran, P.T.; Ungefroren, H.; Vander Heiden, M.G.; Venkateswaran, V.; Vinay, D.S.; Vlachostergios, P.J.; Wang, Z.; Wellen, K.E.; Whelan, R.L.; Yang, E.S.; Yang, H.; Yang, X.; Yaswen, P.; Yedjou, C.; Yin, X.; Zhu, J.; Zollo, M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol., 2015, 35(Suppl.), S276-S304.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007] [PMID: 26590477]
[13]
Lin, Y.; Wang, F.; Yang, L.J.; Chun, Z.; Bao, J.K.; Zhang, G.L. Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum. Phytochemistry, 2013, 95(95), 242-251.
[http://dx.doi.org/10.1016/j.phytochem.2013.08.008] [PMID: 24042064]
[14]
Li, R.; Liu, T.; Liu, M.; Chen, F.; Liu, S.; Yang, J. Anti-influenza A virus activity of dendrobine and its mechanism of action. J. Agric. Food Chem., 2017, 65(18), 3665-3674.
[http://dx.doi.org/10.1021/acs.jafc.7b00276] [PMID: 28417634]
[15]
Feng, Y.; Jia, B.; Feng, Q.; Zhang, Y.; Chen, Y.; Meng, J. Dendrobine attenuates gestational diabetes mellitus in mice by inhibiting Th17 cells. Basic Clin. Pharmacol. Toxicol., 2021, 128(3), 379-385.
[http://dx.doi.org/10.1111/bcpt.13524] [PMID: 33119198]
[16]
Gong, D.Y.; Chen, X.Y.; Guo, S.X.; Wang, B.C.; Li, B. Recent advances and new insights in biosynthesis of dendrobine and sesquiterpenes. Appl. Microbiol. Biotechnol., 2021, 105(18), 6597-6606.
[http://dx.doi.org/10.1007/s00253-021-11534-1] [PMID: 34463801]
[17]
Zheng, S.; Hu, Y.; Zhao, R.; Zhao, T.; Li, H.; Rao, D.; Chun, Z. Quantitative assessment of secondary metabolites and cancer cell inhibiting activity by high performance liquid chromatography fingerprinting in Dendrobium nobile. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2020, 1140, 122017.
[http://dx.doi.org/10.1016/j.jchromb.2020.122017] [PMID: 32050157]
[18]
Song, T.H.; Chen, X.X.; Lee, C.K.; Sze, S.C.; Feng, Y.B.; Yang, Z.J.; Chen, H.Y.; Li, S.T.; Zhang, L.Y.; Wei, G.; Shi, J.; Xu, K.; Ng, T.B.; Zhu, L.L.; Zhang, K.Y. Dendrobine targeting JNK stress signaling to sensitize chemotoxicity of cisplatin against non-small cell lung cancer cells in vitro and in vivo. Phytomedicine, 2019, 53, 18-27.
[http://dx.doi.org/10.1016/j.phymed.2018.06.018] [PMID: 30668397]
[19]
Gomes, M.; Teixeira, A.L.; Coelho, A.; Araújo, A.; Medeiros, R. The role of inflammation in lung cancer. Adv. Exp. Med. Biol., 2014, 816, 1-23.
[http://dx.doi.org/10.1007/978-3-0348-0837-8_1] [PMID: 24818717]
[20]
Duan, M.C.; Han, W.; Jin, P.W.; Wei, Y.P.; Wei, Q.; Zhang, L.M.; Li, J.C. Disturbed Th17/Treg balance in patients with non-small cell lung cancer. Inflammation, 2015, 38(6), 2156-2165.
[http://dx.doi.org/10.1007/s10753-015-0198-x] [PMID: 26077695]
[21]
Korn, T.; Bettelli, E.; Oukka, M.; Kuchroo, V.K. IL-17 and Th17 cells. Annu. Rev. Immunol., 2009, 27(1), 485-517.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132710] [PMID: 19132915]
[22]
Ohkura, N.; Hamaguchi, M.; Morikawa, H.; Sugimura, K.; Tanaka, A.; Ito, Y.; Osaki, M.; Tanaka, Y.; Yamashita, R.; Nakano, N.; Huehn, J.; Fehling, H.J.; Sparwasser, T.; Nakai, K.; Sakaguchi, S. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity, 2012, 37(5), 785-799.
[http://dx.doi.org/10.1016/j.immuni.2012.09.010] [PMID: 23123060]
[23]
Matsumoto, M.; Nakajima, W.; Seike, M.; Gemma, A.; Tanaka, N. Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells. Biochem. Biophys. Res. Commun., 2016, 473(2), 490-496.
[http://dx.doi.org/10.1016/j.bbrc.2016.03.053] [PMID: 26996126]
[24]
Beier, U.H. Apoptotic regulatory T cells retain suppressive function through adenosine. Cell Metabol., 2018, 27(1), 5-7.
[http://dx.doi.org/10.1016/j.cmet.2017.12.013]
[25]
Huang, Y.; Li, L.; Liu, W.; Tang, T.; Chen, L. The progress of CAR-T therapy in cancer and beyond. STEMedicine, 2020, 1(3), e47.
[http://dx.doi.org/10.37175/stemedicine.v1i3.47]
[26]
Ye, J.; Livergood, R.S.; Peng, G. The role and regulation of human Th17 cells in tumor immunity. Am. J. Pathol., 2013, 182(1), 10-20.
[http://dx.doi.org/10.1016/j.ajpath.2012.08.041] [PMID: 23159950]
[27]
Katiyar, S.K.; Meeran, S.M.; Katiyar, N.; Akhtar, S. p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol. Carcinog., 2009, 48(1), 24-37.
[http://dx.doi.org/10.1002/mc.20453] [PMID: 18459128]
[28]
Klatt, N.R.; Brenchley, J.M. Th17 cell dynamics in HIV infection. Curr. Opin. HIV AIDS, 2010, 5(2), 135-140.
[http://dx.doi.org/10.1097/COH.0b013e3283364846] [PMID: 20543590]
[29]
Chevalier, M.F.; Weiss, L. The split personality of regulatory T cells in HIV infection. Blood, 2013, 121(1), 29-37.
[http://dx.doi.org/10.1182/blood-2012-07-409755] [PMID: 23043072]

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