Delphinidin Reduces Cell Proliferation and Induces Apoptosis of Non-Small-Cell Lung Cancer Cells by Targeting EGFR/VEGFR2 Signaling Pathways

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Pal, Harish Chandra ^a   Sharma, Samriti ^a   Strickland, Leah Ray ^a   Agarwal, Jyoti ^a   Athar, Mohammad ^a   Elmets, Craig A ^a   Afaq, Farrukh ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN D1; CYCLINE; DELPHINIDIN; EPIDERMAL GROWTH FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; PROTEIN MCL 1; VASCULOTROPIN RECEPTOR 2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER GROWTH; CANCER INHIBITION; CELL PROLIFERATION; CONCENTRATION RESPONSE; DRUG POTENCY; DRUG TARGETING; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FEMALE; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; PROTEIN EXPRESSION; TUMOR VASCULARIZATION; UPREGULATION;

ANIMALS; ANTHOCYANINS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; CARCINOMA, NON-SMALL-CELL LUNG; CASPASES; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN D1; DISEASE MODELS, ANIMAL; EPIDERMAL GROWTH FACTOR; FEMALE; HUMANS; LUNG NEOPLASMS; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; POLY(ADP-RIBOSE) POLYMERASES; PROLIFERATING CELL NUCLEAR ANTIGEN; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; TUMOR BURDEN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84885076485     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0077270     Document Type: Article

References (52)

1. Siegel R, Jemal A, (2013) American Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society.
2. Sharma SV, Bell DW, Settleman J, Haber DA, (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7: 169-181. doi:10.1038/nrc2088. PubMed: 17318210.
3. Herbst RS, Heymach JV, Lippman SM, (2008) Lung cancer. N Engl J Med 359: 1367-1380. doi:10.1056/NEJMra0802714. PubMed: 18815398.
4. Citri A, Yarden Y, (2006) EGF-ERBB signaling: towards the systems level. Nat Rev Cell Biol 7: 505-516. doi:10.1038/nrm1962.
5. Thelemann A, Petti F, Griffin G, Iwata K, Hunt T, et al. (2005) Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells. Mol Cell Proteomics 4: 356-376. doi:10.1074/mcp.M400118-MCP200. PubMed: 15657067.
6. Hirsch FR, Varella-Garcia M, Cappuzzo F, (2009) Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer. Oncogene 28: S32-S37. doi:10.1038/onc.2009.199. PubMed: 19680294.
7. Gazdar AF, (2010) Epidermal growth factor receptor inhibition in lung cancer: the evolving role of individualized therapy. Cancer Metastasis Rev 29: 37-48. doi:10.1007/s10555-010-9201-z. PubMed: 20127143.
8. Ferrero JM, Ramaioli A, Largillier R, Formento JL, Francoual M, et al. (2001) Epidermal growth factor receptor expression in 780 breast cancer patients: a reappraisal of the prognostic value based on an eight-year median follow-up. Ann Oncol 12: 841-846. doi:10.1023/A:1011183421477. PubMed: 11484962.
9. Ferrara N, Gerber HP, LeCouter J, (2003) The biology of VEGF and its receptors. Nat Med 9: 669-675. doi:10.1038/nm0603-669. PubMed: 12778165.
10. Kalyankrishna S, Grandis JR, (2006) Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol 24: 2666-2672. doi:10.1200/JCO.2005.04.8306. PubMed: 16763281.
11. Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, et al. (2011) Increased VEGFR-2 gene copy is associated with chemoresistance and shorter survival in patients with non-small-cell lung carcinoma who receive adjuvant chemotherapy. Cancer Res 71: 5512-5521. doi:10.1158/0008-5472.CAN-10-2614. PubMed: 21724587.
12. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, et al. (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273: 30336-30343. doi:10.1074/jbc.273.46.30336. PubMed: 9804796.
13. Takahashi T, Ueno H, Shibuya M, (1999) VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 18: 2221-2230. doi:10.1038/sj.onc.1202527. PubMed: 10327068.
14. Mazza G, (1995) Anthocyanins in grapes and grape products. Crit Rev Food Sci Nutr 35: 341-371. doi:10.1080/10408399509527704. PubMed: 7576162.
15. Noda Y, Kaneyuki T, Mori A, Packer L, (2002) Antioxidant activities of Pomegrante Fruit Extract and Its Anthocyanidins: Delphinidin, Cyanidin, and Pelargonidin. J Agric Food Chem 50: 166-171. PubMed: 11754562.
16. Seong AR, Yoo JY, Choi K, Lee MH, Lee YH, et al. (2011) Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-κB acetylation in fibroblast-like synoviocyte MH7A cells. Biochem Biophys Res Commun 410: 581-586. doi:10.1016/j.bbrc.2011.06.029. PubMed: 21683061.
17. Haseeb A, Chen D, Haqqi TM, (2013) Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1(Ser376) in human articular chondrocytes. Rheumatology (Oxford) 52: 998-1008.
18. Syed DN, Afaq F, Sarfaraz S, Khan N, Kedlaya R, et al. (2008) Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol 231: 52-60. doi:10.1016/j.taap.2008.03.023. PubMed: 18499206.
19. Hafeez BB, Siddiqui IA, Asim M, Malik A, Afaq F, et al. (2008) A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-kappaB signaling. Cancer Res 68: 8564-8572. doi:10.1158/0008-5472.CAN-08-2232. PubMed: 18922932.
20. Afaq F, Zaman N, Khan N, Syed DN, Sarfaraz S, et al. (2008) Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables. Int J Cancer 123: 1508-1515. doi:10.1002/ijc.23675. PubMed: 18623129.
21. Yarden Y, Sliwkowski MX, (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2: 127-137. doi:10.1038/35052073. PubMed: 11252954.
22. Sharma SV, Settleman J, (2009) ErbBs in lung cancer. Exp Cell Res 315: 557-571. doi:10.1016/j.yexcr.2008.07.026. PubMed: 18721806.
23. Silva SR, Bowen KA, Rychahou PG, Jackson LN, Weiss HL, et al. (2011) VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis. Int J Cancer 128: 1045-1056. doi:10.1002/ijc.25441. PubMed: 20473929.
24. Chatterjee S, Heukamp LC, Siobal M, Schöttle J, Wieczorek C, et al. (2013) Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer. J Clin Invest 123: 1732-1740. doi:10.1172/JCI65385. PubMed: 23454747.
25. Yarden Y, Pines G, (2012) The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer 12: 553-563. doi:10.1038/nrc3309. PubMed: 22785351.
26. Wheeler DL, Dunn EF, Harari PM, (2010) Understanding resistance to EGFR inhibitors - impact on future treatment strategies. Nat Rev Clin Oncol 7: 493-507. doi:10.1038/nrclinonc.2010.97. PubMed: 20551942.
27. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF, (2008) The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 8: 187-198. doi:10.2174/156800908784293659. PubMed: 18473732.
28. Mueller KL, Powell K, Madden JM, Eblen ST, Boerner JL, (2010) EGFR Tyrosine 845 hosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK. Transl Oncology 5: 327-334.
29. Wagner EF, Nebreda AR, (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9: 537-549. doi:10.1038/nrc2694. PubMed: 19629069.
30. Roberts PJ, Der CJ, (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26: 3291-3210. doi:10.1038/sj.onc.1210422. PubMed: 17496923.
31. Kobayashi S, Shimamura T, Monti S, Steidl U, Hetherington CJ, et al. (2006) Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res 66: 11389-11398. doi:10.1158/0008-5472.CAN-06-2318. PubMed: 17145885.
32. Moldovan GL, Pfander B, Jentsch S, (2007) PCNA, the maestro of the replication fork. Cell 129: 665-679. doi:10.1016/j.cell.2007.05.003. PubMed: 17512402.
33. Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, et al. (2006) Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol 8: 1359-1368. doi:10.1038/ncb1501. PubMed: 17115032.
34. Earnshaw WC, Martins LM, Kaufmann SH, (2006) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68: 383-324. PubMed: 10872455.
35. Jimeno A, Hidalgo M, (2006) Pharmacogenomics of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Biochim Biophys Acta 1766: 217-229. PubMed: 17045403.
36. Arteaga CL, (2002) Epidermal Growth Factor Receptor Dependence in Human Tumors: More Than Just Expression? Oncologist 7: 31-39. doi:10.1634/theoncologist.7-suppl_4-31. PubMed: 12202786.
37. Ferrara N, (2004) Vascular Enothelial Growth Factor as a Target for Anticancer Therapy. Oncologist 9: 2-10. doi:10.1634/theoncologist.9-suppl_1-2. PubMed: 15178810.
38. Tabernero J, (2007) The role of VEGF and EGFR inhibition: Implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 5: 203-220. doi:10.1158/1541-7786.MCR-06-0404. PubMed: 17374728.
39. Pennell NA, Lynch TJ Jr, (2009) Combined inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC. Oncologist 14: 399-411. doi:10.1634/theoncologist.2008-0276. PubMed: 19357226.
40. Cerniglia GJ, Pore N, Tsai JH, Schultz S, Mick R, et al. (2009) Epidermal Growth Factor Receptor Inhibition Modulates the Microenvironment by Vascular Normalization to Improve Chemotherapy and Radiotherapy Efficacy. PLOS ONE 4: e6539. doi:10.1371/journal.pone.0006539. PubMed: 19657384.
41. Zhang X, Li Y, Li H, Qin Y, Bai C, et al. (2012) Combined EGFR and VEGFR versus Single EGFR Signaling Pathways Inhibition Therapy for NSCLC: A Systematic Review and Meta-Analysis. PLOS ONE 7: e40178. doi:10.1371/journal.pone.0040178. PubMed: 22916093.
42. Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, et al. (2011) Increased VEGFR-2 gene copy is associated with chemoresistance and shorter survival in patients with non-small-cell lung carcinoma who receive adjuvant chemotherapy. Cancer Res 71: 5512-5521. doi:10.1158/0008-5472.CAN-10-2614. PubMed: 21724587.
43. Ciardiello F, Troiani T, Bianco R, Orditura M, Morgillo F, (2006) Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy. Ann Oncol 17: 109-114. PubMed: 16760272.
44. Naumov GN, Nilsson MB, Cascone T, Briggs A, Straume O, et al. (2009) Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res 15: 3484-3494. doi:10.1158/1078-0432.CCR-08-2904. PubMed: 19447865.
45. Engelman JA, Jänne PA, Mermel C, Pearlberg J, Mukohara T, et al. (2005) ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci U S A 102: 3788-3793. doi:10.1073/pnas.0409773102. PubMed: 15731348.
46. Faber AC, Li D, Song Y, Liang MC, Yeap BY, et al. (2009) Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc Natl Acad Sci U S A 106: 19503-19508. doi:10.1073/pnas.0905056106. PubMed: 19850869.
47. Engelman JA, (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9: 550-562. doi:10.1038/nrc2664. PubMed: 19629070.
48. Huang WC, Hung MC, (2009) Induction of Akt activity by chemotherapy confers acquired resistance. J Formos Med Assoc 108: 180-194. doi:10.1016/S0929-6646(09)60051-6. PubMed: 19293033.
49. Corcoran RB, Ebi H, Turke AB, Coffee EM, Nishino M, et al. (2012) EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2: 227-235. doi:10.1158/2159-8290.CD-11-0341 PubMed: 22448344.
50. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, et al. (2012) Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 16: 15-31. doi:10.1517/14728222.2011.648617. PubMed: 22239438.
51. Arteaga CL, (2001) The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J Clin Oncol 19: 32S-40S. PubMed: 11560969.
52. Bussink J, Vander-Kogel AJ, Kaanders JH, (2008) Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol 9: 288-296. doi:10.1016/S1470-2045(08)70073-1. PubMed: 18308254.