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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Research

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy

Authors: Afshin Amini, Samar Masoumi-Moghaddam, Anahid Ehteda, David Lawson Morris

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

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Abstract

Background

Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored.

Methods

The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay.

Results

Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy.

Conclusion

We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from cell cycle arrest, apoptosis and autophagy. Towards the development of novel strategies for the enhancement of microscopic cytoreduction, our results lay the basis for further evaluation of this formulation in locoregional approaches to peritoneal surface malignancies and carcinomatosis.
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Literature
1.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127: 2893-2917. 10.1002/ijc.25516.CrossRefPubMed
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
3.
Sugarbaker PH: Peritoneum as the first-line of defense in carcinomatosis. J Surg Oncol. 2007, 95: 93-96. 10.1002/jso.20676.CrossRefPubMed
4.
Sugarbaker PH: Cytoreductive surgery and intraperitoneal chemotherapy with peritoneal spread of cystadenocarcinoma. Eur J Surg Suppl. 1991, 561: 75-82.PubMed
5.
Sugarbaker PH: Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome. Eur J Surg Oncol. 2001, 27: 239-243. 10.1053/ejso.2000.1038.CrossRefPubMed
6.
Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN, Baratti D, Deraco M, Elias D, Sardi A, Liauw W, Yan TD, Barrios P, Gomez Portilla A, de Hingh IH, Ceelen WP, Pelz JO, Piso P, Gonzalez-Moreno S, Van Der Speeten K, Morris DL: Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012, 30: 2449-2456. 10.1200/JCO.2011.39.7166.CrossRefPubMed
7.
Chua TC, Liauw W, Morris DL: The St George Hospital Peritoneal Surface Malignancy Program-where are we now?. ANZ J Surg. 2009, 79: 416-418. 10.1111/j.1445-2197.2009.04946.x.CrossRefPubMed
8.
Chua TC, Martin S, Saxena A, Liauw W, Yan TD, Zhao J, Lok I, Morris DL: Evaluation of the cost-effectiveness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (peritonectomy) at the St George Hospital peritoneal surface malignancy program. Ann Surg. 2010, 251: 323-329. 10.1097/SLA.0b013e3181c9b53c.CrossRefPubMed
9.
Pillai K, Akhter J, Chua TC, Morris DL: A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei. Int J Cancer. 2014, 134: 478-486. 10.1002/ijc.28380.CrossRefPubMed
10.
Houck JC, Chang CM, Klein G: Isolation of an effective debriding agent from the stems of pineapple plants. Int J Tissue React. 1983, 5: 125-134.PubMed
11.
Hale LP, Greer PK, Trinh CT, James CL: Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005, 5: 783-793. 10.1016/j.intimp.2004.12.007.CrossRefPubMed
12.
Taussig SJ, Batkin S: Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988, 22: 191-203. 10.1016/0378-8741(88)90127-4.CrossRefPubMed
13.
Maurer HR: Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001, 58: 1234-1245. 10.1007/PL00000936.CrossRefPubMed
14.
Bromelain. Monograph. Altern Med Rev. 2010, 15: 361-368.
15.
Chobotova K, Vernallis AB, Majid FA: Bromelain’s activity and potential as an anti-cancer agent: current evidence and perspectives. Cancer Lett. 2010, 290: 148-156. 10.1016/j.canlet.2009.08.001.CrossRefPubMed
16.
Hurst GA, Shaw PB, LeMaistre CA: Laboratory and clinical evaluation of the mucolytic properties of acetylcysteine. Am Rev Respir Dis. 1967, 96: 962-970.PubMed
17.
Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT: Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977, 2: 432-434. 10.1016/S0140-6736(77)90612-2.CrossRefPubMed
18.
Millea PJ: N-acetylcysteine: multiple clinical applications. Am Fam Physician. 2009, 80: 265-269.PubMed
19.
Rushworth GF, Megson IL: Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014, 141: 150-159. 10.1016/j.pharmthera.2013.09.006.CrossRefPubMed
20.
Matsuda K, Yamauchi K, Matsumoto T, Sano K, Yamaoka Y, Ota H: Quantitative analysis of the effect of Helicobacter pylori on the expressions of SOX2, CDX2, MUC2, MUC5AC, MUC6, TFF1, TFF2, and TFF3 mRNAs in human gastric carcinoma cells. Scand J Gastroenterol. 2008, 43: 25-33. 10.1080/00365520701579795.PubMedCentralCrossRefPubMed
21.
Leteurtre E, Gouyer V, Rousseau K, Moreau O, Barbat A, Swallow D, Huet G, Lesuffleur T: Differential mucin expression in colon carcinoma HT-29 clones with variable resistance to 5-fluorouracil and methotrexate. Biol Cell. 2004, 96: 145-151. 10.1016/j.biolcel.2003.12.005.CrossRefPubMed
22.
van Klinken BJ-W, Oussoren E, Weenink J-J, Strous G, Büller H, Dekker J, Einerhand AC: The human intestinal cell lines Caco-2 and LS174T as models to study cell-type specific mucin expression. Glycoconj J. 1996, 13: 757-768. 10.1007/BF00702340.CrossRefPubMed
23.
Taussig SJ, Szekerczes J, Batkin S: Inhibition of tumour growth in vitro by bromelain, an extract of the pineapple plant (Ananas comosus). Planta Med. 1985, 51: 538-539. 10.1055/s-2007-969596.CrossRefPubMed
24.
Grabowska E, Eckert K, Fichtner I, Schulzeforster K, Maurer H: Bromelain proteases suppress growth, invasion and lung metastasis of B16F10 mouse melanoma cells. Int J Oncol. 1997, 11: 243-248.PubMed
25.
Beuth J, Braun JM: Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.). In Vivo. 2005, 19: 483-485.PubMed
26.
Baez R, Lopes MT, Salas CE, Hernandez M: In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. Planta Med. 2007, 73: 1377-1383. 10.1055/s-2007-990221.CrossRefPubMed
27.
Amini A, Ehteda A, Masoumi Moghaddam S, Akhter J, Pillai K, Morris DL: Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). Oncol Targets Ther. 2013, 6: 403-409.
28.
Romano B, Fasolino I, Pagano E, Capasso R, Pace S, De Rosa G, Milic N, Orlando P, Izzo AA, Borrelli F: The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects. Mol Nutr Food Res. 2014, 58: 457-465. 10.1002/mnfr.201300345.CrossRefPubMed
29.
Tysnes BB, Maurer HR, Porwol T, Probst B, Bjerkvig R, Hoover F: Bromelain reversibly inhibits invasive properties of glioma cells. Neoplasia. 2001, 3: 469-479. 10.1038/sj.neo.7900196.PubMedCentralCrossRefPubMed
30.
Bhui K, Tyagi S, Prakash B, Shukla Y: Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. Biofactors. 2010, 36: 474-482. 10.1002/biof.121.CrossRefPubMed
31.
Paroulek AF, Jaffe M, Rathinavelu A: The effects of the herbal enzyme bromelain against breast cancer cell line GI101A. FASEB J 2009, 23:LB18.,
32.
Dhandayuthapani S, Perez HD, Paroulek A, Chinnakkannu P, Kandalam U, Jaffe M, Rathinavelu A: Bromelain-induced apoptosis in GI-101A breast cancer cells. J Med Food. 2012, 15: 344-349. 10.1089/jmf.2011.0145.CrossRefPubMed
33.
Bhui K, Tyagi S, Srivastava AK, Singh M, Roy P, Singh R, Shukla Y: Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis. Mol Carcinog. 2012, 51: 231-243. 10.1002/mc.20769.CrossRefPubMed
34.
Pillai K, Ehteda A, Akhter J, Chua TC, Morris DL: Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells. Anticancer Drugs. 2014, 25: 150-160. 10.1097/CAD.0000000000000039.CrossRefPubMed
35.
Maurer HR, Hozumi M, Honma Y, Okabe-Kado J: Bromelain induces the differentiation of leukemic cells in vitro: an explanation for its cytostatic effects?. Planta Med. 1988, 54: 377-381. 10.1055/s-2006-962475.CrossRefPubMed
36.
Goldstein N, Taussig SJ, Gallup JD, Koto V: Bromelain as a skin cancer preventive in hairless mice. Hawaii Med J. 1975, 34: 91-94.PubMed
37.
Kalra N, Bhui K, Roy P, Srivastava S, George J, Prasad S, Shukla Y: Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicol Appl Pharmacol. 2008, 226: 30-37. 10.1016/j.taap.2007.08.012.CrossRefPubMed
38.
Bhui K, Prasad S, George J, Shukla Y: Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett. 2009, 282: 167-176. 10.1016/j.canlet.2009.03.003.CrossRefPubMed
39.
Gerard G: Anticancer treatment and bromelains. Agressologie. 1972, 13: 261-274.PubMed
40.
Nieper HA: Bromelain in der Kontrolle malignen Wachstums. Krebsgeschehen. 1976, 1: 9-15.
41.
Zavadova E, Desser L, Mohr T: Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. Cancer Biother. 1995, 10: 147-152. 10.1089/cbr.1995.10.147.CrossRefPubMed
42.
Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer HR: Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. Oncol Rep. 1999, 6: 1191-1199.PubMed
43.
Nargi JL, Ratan RR, Griffin DE: p53-independent inhibition of proliferation and p21(WAF1/Cip1)-modulated induction of cell death by the antioxidants N-acetylcysteine and vitamin E. Neoplasia. 1999, 1: 544-556. 10.1038/sj.neo.7900068.PubMedCentralCrossRefPubMed
44.
Kawakami S, Kageyama Y, Fujii Y, Kihara K, Oshima H: Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells. Anticancer Res. 2001, 21: 213-219.PubMed
45.
Supabphol A, Muangman V, Chavasiri W, Supabphol R, Gritsanapan W: N-acetylcysteine inhibits proliferation, adhesion, migration and invasion of human bladder cancer cells. J Med Assoc Thai. 2009, 92: 1171-1177.PubMed
46.
Lee YJ, Lee DM, Lee CH, Heo SH, Won SY, Im JH, Cho MK, Nam HS, Lee SH: Suppression of human prostate cancer PC-3 cell growth by N-acetylcysteine involves over-expression of Cyr61. Toxicol In Vitro. 2011, 25: 199-205. 10.1016/j.tiv.2010.10.020.CrossRefPubMed
47.
Lee MF, Chan CY, Hung HC, Chou IT, Yee AS, Huang CY: N-acetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer. Oral Oncol. 2013, 49: 129-135. 10.1016/j.oraloncology.2012.08.003.CrossRefPubMed
48.
Hann SS, Zheng F, Zhao S: Targeting 3-phosphoinositide-dependent protein kinase 1 by N-acetyl-cysteine through activation of peroxisome proliferators activated receptor alpha in human lung cancer cells, the role of p53 and p65. J Exp Clin Cancer Res 2013, 32:43.,
49.
De Flora S, Bennicelli C, Zanacchi P, Camoirano A, Morelli A, De Flora A: In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens. Carcinogenesis. 1984, 5: 505-510. 10.1093/carcin/5.4.505.CrossRefPubMed
50.
De Flora S, Bennicelli C, Camoirano A, Serra D, Romano M, Rossi GA, Morelli A, De Flora A: In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. Carcinogenesis. 1985, 6: 1735-1745. 10.1093/carcin/6.12.1735.CrossRefPubMed
51.
Martinez E, Domingo P: N-acetylcysteine as chemoprotectant in cancer chemotherapy. Lancet 1991, 338:249.,
52.
Pendyala L, Creaven PJ: Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Cancer Epidemiol Biomarkers Prev. 1995, 4: 245-251.PubMed
53.
Estensen RD, Levy M, Klopp SJ, Galbraith AR, Mandel JS, Blomquist JA, Wattenberg LW: N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. 1999, 147: 109-114. 10.1016/S0304-3835(99)00281-5.CrossRefPubMed
54.
van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H: EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst. 2000, 92: 977-986. 10.1093/jnci/92.12.977.CrossRefPubMed
55.
Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S: Prenatal N-acetylcysteine prevents cigarette smoke-induced lung cancer in neonatal mice. Carcinogenesis. 2009, 30: 1398-1401. 10.1093/carcin/bgp128.PubMedCentralCrossRefPubMed
56.
Berrigan MJ, Gurtoo HL, Sharma SD, Struck RF, Marinello AJ: Protection by N-acetylcysteine of cyclophosphamide metabolism - related in vivo depression of mixed function oxygenase activity and in vitro denaturation of cytochrome P-450. Biochem Biophys Res Commun. 1980, 93: 797-803. 10.1016/0006-291X(80)91147-X.CrossRefPubMed
57.
Lin PC, Lee MY, Wang WS, Yen CC, Chao TC, Hsiao LT, Yang MH, Chen PM, Lin KP, Chiou TJ: N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer. 2006, 14: 484-487. 10.1007/s00520-006-0018-9.CrossRefPubMed
58.
Luo J, Tsuji T, Yasuda H, Sun Y, Fujigaki Y, Hishida A: The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats. Nephrol Dial Transplant. 2008, 23: 2198-2205. 10.1093/ndt/gfn090.CrossRefPubMed
59.
Al-Tonbary Y, Al-Haggar M, El-Ashry R, El-Dakroory S, Azzam H, Fouda A: Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Adv Hematol 2009, 2009:689639.,
60.
Riga MG, Chelis L, Kakolyris S, Papadopoulos S, Stathakidou S, Chamalidou E, Xenidis N, Amarantidis K, Dimopoulos P, Danielides V: Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy. Am J Clin Oncol. 2013, 36: 1-6. 10.1097/COC.0b013e31822e006d.CrossRefPubMed
61.
Yoo J, Hamilton SJ, Angel D, Fung K, Franklin J, Parnes LS, Lewis D, Venkatesan V, Winquist E: Cisplatin otoprotection using transtympanic L-N-acetylcysteine: a pilot randomized study in head and neck cancer patients. Laryngoscope. 2014, 124: E87-E94. 10.1002/lary.24360.CrossRefPubMed
62.
Bach SP, Williamson SE, Marshman E, Kumar S, O’Dwyer ST, Potten CS, Watson AJ: The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice. J Gastrointest Surg. 2001, 5: 91-97. 10.1016/S1091-255X(01)80018-4.CrossRefPubMed
63.
Brum G, Carbone T, Still E, Correia V, Szulak K, Calianese D, Best C, Cammarata G, Higgins K, Ji F, Di W, Wan Y: N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. Int J Oncol. 2013, 42: 211-218.PubMedCentralPubMed
64.
Kretzmann NA, Chiela E, Matte U, Marroni N, Marroni CA: N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells. Comp Hepatol 2012, 11:4.,
65.
Zheng J, Lou JR, Zhang XX, Benbrook DM, Hanigan MH, Lind SE, Ding WQ: N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death. Cancer Lett. 2010, 298: 186-194. 10.1016/j.canlet.2010.07.003.CrossRefPubMed
66.
Lambert JD, Sang S, Yang CS: N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct. Free Radic Biol Med. 2008, 44: 1069-1074. 10.1016/j.freeradbiomed.2007.12.016.PubMedCentralCrossRefPubMed
67.
Sceneay J, Liu MC, Chen A, Wong CS, Bowtell DD, Moller A: The antioxidant N-acetylcysteine prevents HIF-1 stabilization under hypoxia in vitro but does not affect tumorigenesis in multiple breast cancer models in vivo . PLoS One 2013, 8:e66388.,
68.
Satyanarayana A, Kaldis P: Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene. 2009, 28: 2925-2939. 10.1038/onc.2009.170.CrossRefPubMed
69.
Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720.PubMedCentralCrossRefPubMed
70.
De Flora S, Izzotti A, D’Agostini F, Balansky RM: Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis. 2001, 22: 999-1013. 10.1093/carcin/22.7.999.CrossRefPubMed
71.
Huang TS, Duyster J, Wang JY: Biological response to phorbol ester determined by alternative G1 pathways. Proc Natl Acad Sci U S A. 1995, 92: 4793-4797. 10.1073/pnas.92.11.4793.PubMedCentralCrossRefPubMed
72.
Arora-Kuruganti P, Lucchesi PA, Wurster RD: Proliferation of cultured human astrocytoma cells in response to an oxidant and antioxidant. J Neurooncol. 1999, 44: 213-221. 10.1023/A:1006315332098.CrossRefPubMed
73.
Kurata S: Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. J Biol Chem. 2000, 275: 23413-23416. 10.1074/jbc.C000308200.CrossRefPubMed
74.
Liu M, Wikonkal NM, Brash DE: Induction of cyclin-dependent kinase inhibitors and G(1) prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis. 1999, 20: 1869-1872. 10.1093/carcin/20.9.1869.CrossRefPubMed
75.
Tsai JC, Jain M, Hsieh CM, Lee WS, Yoshizumi M, Patterson C, Perrella MA, Cooke C, Wang H, Haber E, Schlegel R, Lee ME: Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells. J Biol Chem. 1996, 271: 3667-3670. 10.1074/jbc.271.7.3667.CrossRefPubMed
76.
Liu M, Pelling JC, Ju J, Chu E, Brash DE: Antioxidant action via p53-mediated apoptosis. Cancer Res. 1998, 58: 1723-1729.PubMed
77.
Havre PA, O’Reilly S, McCormick JJ, Brash DE: Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine. Cancer Res. 2002, 62: 1443-1449.PubMed
78.
Cho SG, Woo SM, Ko SG: Butein suppresses breast cancer growth by reducing a production of intracellular reactive oxygen species. J Exp Clin Cancer Res 2014, 33:51.,
79.
Lepri E, Gambelunghe C, Fioravanti A, Pedini M, Micheletti A, Rufini S: N-acetylcysteine increases apoptosis induced by H(2) O(2) and mo-antiFas triggering in a 3DO hybridoma cell line. Cell Biochem Funct. 2000, 18: 201-208. 10.1002/1099-0844(200009)18:3<201::AID-CBF873>3.0.CO;2-A.CrossRefPubMed
80.
Rieber M, Rieber MS: N-Acetylcysteine enhances UV-mediated caspase-3 activation, fragmentation of E2F-4, and apoptosis in human C8161 melanoma: inhibition by ectopic Bcl-2 expression. Biochem Pharmacol. 2003, 65: 1593-1601. 10.1016/S0006-2952(03)00147-3.CrossRefPubMed
81.
Deshpande VS, Kehrer JP: Mechanisms of N-acetylcysteine-driven enhancement of MK886-induced apoptosis. Cell Biol Toxicol. 2006, 22: 303-311. 10.1007/s10565-006-0072-6.CrossRefPubMed
Metadata
Title
Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy
Authors
Afshin Amini
Samar Masoumi-Moghaddam
Anahid Ehteda
David Lawson Morris
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-014-0092-7

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