| Infectious Agents and Cancer | |
| Inhibitory effect of (−)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancer MiaPaca-2 cell growth | |
| Francesco Izzo1  Claudio Arra2  Antonella Petrillo3  Vincenza Granata3  Aurelio Nasto1  Raimondo Di Giacomo1  Alfonso Amore1  Mauro Piccirillo1  Vittorio Albino1  Massimiliano Barbieri1  Vitale Del Vecchio2  Antonio Barbieri2  Maddalena Leongito1  Sabrina Bimonte1  | |
| [1] Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori “Fondazione G. Pascale”, − IRCCS - Via Mariano Semmola, Naples, 80131, Italy;S.S.D Sperimentazione Animale, Istituto Nazionale per lo studio e la cura dei Tumori “Fondazione G. Pascale”, − IRCCS - Via Mariano Semmola, Naples, 80131, Italy;Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori “Fondazione G. Pascale”, − IRCCS - Via Mariano Semmola, Naples, 80131, Italy | |
| 关键词: Apoptosis; Cell proliferation; Bleomycin; Pancreatic cancer; (−)-Epigallocatechin-3-gallate; | |
| Others : 1221521 DOI : 10.1186/s13027-015-0016-y |
|
| received in 2015-05-19, accepted in 2015-06-26, 发布年份 2015 | |
PDF
|
|
【 摘 要 】
Background
Human pancreatic cancer is currently one of the deadliest cancers with high mortality rate. It has been previously shown that (−)-epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has showed suppressive effects on human pancreatic cancer cells. Bleomycin, (BLM), an anti-cancer chemotherapeutic drug that induces DNA damage, has antitumor effects by induction of apoptosis in several cancer cell lines and also in pancreatic cancer cells. The present study investigated for the first time, the inhibitory effect of EGCG and BLM on pancreatic cancer cell growth.
Methods
Using the pancreatic cancer cell lines MIA PaCa-2 cells the efficacy and synergism of EGCG and BLM were evaluated by in vitro tests. Inhibition of cell proliferation was determined by MTT assay. Mitochondrial depolarization was performed with JC-1 probe. Viability and apoptosis were determined by Flow Cytometry with annexin V, propidium iodide staining and DNA fragmentation assay.
Results
Cell proliferation assay revealed significant additive inhibitory effects with combination of EGCG and BLM at 72 h in a dose dependent manner. The combination of EGCG and BLM induced cell cycle S-phase arrest and mitochondrial depolarization. Viability, apoptosis and DNA fragmentation assay indicated that the combination of EGCG and bleomycin potentiated apoptosis.
Conclusions
Our results indicate that EGCG and BLM have additive anti-proliferative effects in vitro by induction of apoptosis of MIA PaCa-2 cells. This combination could represent a new strategy with potential advantages for treatment of pancreatic cancer. To date, this is the first report published of the inhibitory effect of EGCG and BLM on human pancreatic cancer MIA Paca-2 cell growth.
【 授权许可】
2015 The Author(s).
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20150801090834773.pdf | 1053KB | ||
| Fig. 3. | 27KB | Image | |
| Figure 6. | 44KB | Image | |
| Fig. 1. | 51KB | Image |
【 图 表 】
Fig. 1.
Figure 6.
Fig. 3.
【 参考文献 】
- [1]Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al.: Cancer statistics, 2006. CA Cancer J Clin 2006, 56(2):106-30.
- [2]Granata V, Fusco R, Piccirillo M, Palaia R, Petrillo A, Izzo F. Electrochemotherapy in locally advanced pancreatic cancer: Preliminary results. Int J Surg. 2015;24.
- [3]Jaidev LR, Krishnan UM, Sethuraman S: Gemcitabine loaded biodegradable PLGA nanospheres for in vitro pancreatic cancer therapy. Mater Sci Eng C Mater Biol Appl. 2015, 47:40-7.
- [4]Leone F, Gatti M, Massucco P, Colombi F, Sperti E, Campanella D, et al.: Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer 2013, 119(2):277-84.
- [5]Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997, 15(6):2403-13.
- [6]Li D, Xie K, Wolff R, Abbruzzese JL: Pancreatic cancer. Lancet 2004, 363(9414):1049-57.
- [7]Bimonte S, Barbieri A, Palma G, Luciano A, Rea D, Arra C: Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. Biomed Res Int. 2013, 2013:810423.
- [8]Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB: Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 2007, 67(8):3853-61.
- [9]Fiala M: Curcumin and omega-3 fatty acids enhance NK cell-induced apoptosis of pancreatic cancer cells but curcumin inhibits interferon-gamma production: benefits of omega-3 with curcumin against cancer. Molecules 2015, 20(2):3020-6.
- [10]Zhou D, Ding N, Zhao S, Li D, Van Doren J, Qian Y, et al.: Synthesis and evaluation of curcumin-related compounds containing inden-2-one for their effects on human cancer cells. Biol Pharm Bull 2014, 37(12):1977-81.
- [11]Kostin SF, McDonald DE, McFadden DW: Inhibitory effects of (−)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro. J Surg Res 2012, 177(2):255-62.
- [12]Shankar S, Ganapathy S, Srivastava RK: Green tea polyphenols: biology and therapeutic implications in cancer. Front Biosci. 2007, 12:4881-99.
- [13]Lambert JD, Yang CS: Mechanisms of cancer prevention by tea constituents. J Nutr 2003, 133(10):3262S-7.
- [14]Yang CS, Wang H: Mechanistic issues concerning cancer prevention by tea catechins. Mol Nutr Food Res 2011, 55(6):819-31.
- [15]Chow HH, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, et al.: Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res 2003, 9(9):3312-9.
- [16]Shammas MA, Neri P, Koley H, Batchu RB, Bertheau RC, Munshi V, et al.: Specific killing of multiple myeloma cells by (−)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood 2006, 108(8):2804-10.
- [17]Shankar S, Suthakar G, Srivastava RK: Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci. 2007, 12:5039-51.
- [18]Shankar S, Marsh L, Srivastava RK: EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Mol Cell Biochem 2013, 372(1–2):83-94.
- [19]Umezawa H, Maeda K, Takeuchi T, Okami Y: New antibiotics, bleomycin A and B. J Antibiot (Tokyo) 1966, 19(5):200-9.
- [20]Einhorn LH: Curing metastatic testicular cancer. Proc Natl Acad Sci U S A 2002, 99(7):4592-5.
- [21]Bayer RA, Gaynor ER, Fisher RI: Bleomycin in non-Hodgkin’s lymphoma. Semin Oncol. 1992, 19(2 Suppl 5):46-52.
- [22]Yu Z, Schmaltz RM, Bozeman TC, Paul R, Rishel MJ, Tsosie KS, et al.: Selective tumor cell targeting by the disaccharide moiety of bleomycin. J Am Chem Soc 2013, 135(8):2883-6.
- [23]Levi JA, Raghavan D, Harvey V, Thompson D, Sandeman T, Gill G, et al.: The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group. J Clin Oncol 1993, 11(7):1300-5.
- [24]Picozzi VJ Jr, Sikic BI, Carlson RW, Koretz M, Ballon SC: Bleomycin, mitomycin, and cisplatin therapy for advanced squamous carcinoma of the uterine cervix: a phase II study of the Northern California Oncology Group. Cancer Treat Rep 1985, 69(7–8):903-5.
- [25]Holmes CE, Carter BJ, Hecht SM: Characterization of iron (II).bleomycin-mediated RNA strand scission. Biochemistry 1993, 32(16):4293-307.
- [26]Kane SA, Hecht SM: Polynucleotide recognition and degradation by bleomycin. Prog Nucleic Acid Res Mol Biol. 1994, 49:313-52.
- [27]Claussen CA, Long EC: Nucleic Acid recognition by metal complexes of bleomycin. Chem Rev 1999, 99(9):2797-816.
- [28]Hecht SM: Bleomycin: new perspectives on the mechanism of action. J Nat Prod 2000, 63(1):158-68.
- [29]Abraham AT, Lin JJ, Newton DL, Rybak S, Hecht SM: RNA cleavage and inhibition of protein synthesis by bleomycin. Chem Biol 2003, 10(1):45-52.
- [30]Chen J, Stubbe J: Bleomycins: towards better therapeutics. Nat Rev Cancer 2005, 5(2):102-12.
- [31]Tao ZF, Konishi K, Keith G, Hecht SM: An efficient mammalian transfer RNA target for bleomycin. J Am Chem Soc 2006, 128(46):14806-7.
- [32]Tang S, Bao H, Zhang Y, Yao J, Yang P, Chen X: 14-3-3epsilon mediates the cell fate decision-making pathways in response of hepatocellular carcinoma to Bleomycin-induced DNA damage. PLoS One 2013., 8(3) Article ID e55268
- [33]Tang S, Bai C, Yang P, Chen X: 14-3-3epsilon boosts bleomycin-induced DNA damage response by inhibiting the drug-resistant activity of MVP. J Proteome Res 2013, 12(6):2511-24.
- [34]Glazyrin AL, Chinni S, Alhasan S, Adsay VN, Vaitkevicius VK, Sarkar FH: Molecular mechanism(s) of actinomycin-D induced sensitization of pancreatic cancer cells to CD95 mediated apoptosis. Int J Oncol 2002, 20(1):201-5.
- [35]Girelli RPS, Cataldo I, Cordo V, Martini L, Scarpa A, Bassi C: Feasibility and safety of electrochemotherapy (ECT) in the pancreas: a pre-clinical investigation. Radiol Oncol. 2015, 49(2):147-54.
- [36]Li Y, Zhang T, Jiang Y, Lee HF, Schwartz SJ, Sun D: (−)-Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line Mia Paca-2. Mol Pharm 2009, 6(4):1152-9.
- [37]Vu HA, Beppu Y, Chi HT, Sasaki K, Yamamoto H, Xinh PT, et al.: Green tea epigallocatechin gallate exhibits anticancer effect in human pancreatic carcinoma cells via the inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor. J Biomed Biotechnol. 2010, 2010:290516.
- [38]Mannal PW, Alosi JA, Schneider JG, McDonald DE, McFadden DW: Pterostilbene inhibits pancreatic cancer in vitro. J Gastrointest Surg 2010, 14(5):873-9.
- [39]Li Y, Shen X, Wang X, Li A, Wang P, Jiang P, et al.: EGCG regulates the cross-talk between JWA and topoisomerase IIalpha in non-small-cell lung cancer (NSCLC) cells. Sci Rep. 2015, 5:11009.
- [40]Hu F, Wei F, Wang Y, Wu B, Fang Y, Xiong B: EGCG synergizes the therapeutic effect of cisplatin and oxaliplatin through autophagic pathway in human colorectal cancer cells. J Pharmacol Sci 2015, 128(1):27-34.
- [41]Wang X, Jiang P, Wang P, Yang CS, Feng Q: EGCG enhances cisplatin sensitivity by regulating expression of the copper and cisplatin influx transporter CTR1 in ovary cancer. PLoS One 2015., 10(4) Article ID e0125402
- [42]Sriram N, Kalayarasan S, Sudhandiran G: Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis. Chem Biol Interact 2009, 180(2):271-80.
PDF